Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Aging of Long‐Lived Proteins: Extracellular Matrix (Collagens, Elastins, Proteoglycans) and Lens Crystallins

David R. Sell, Vincent M. Monnier

10.1002/cphy.cp110110

Source: Supplement 28: Handbook of Physiology, Aging

Originally published: 1995

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Collagens
1.1 Overview
1.2 Methodological Difficulties in the Assessment of Collagen Changes during Aging
1.3 Hypertension and Collagen Deposition in Relation to the Aging Process
1.4 Turnover of Collagen
1.5 Physical Properties of Aging Collagen
1.6 Measurement of the Physical Properties of Collagen as Potential Biomarkers of Aging
1.7 Chemical Properties of Aging Collagen
2 Elastin
2.1 Molecular Contrasts between Elastin and Collagen
2.2 Morphological Changes in Elastin with Aging
2.3 Quantitative Changes in Elastin with Aging
2.4 Conclusions
3 Proteoglycans
3.1 Biochemical Composition
3.2 Aggregating and Nonaggregating Populations of Proteoglycans
3.3 Age‐Related Changes in Proteoglycans
3.4 Conclusions
4 Lens Crystallins
4.1 Overview
4.2 Age‐Related Changes in Lens and Lens Crystallins
4.3 Changes in Enzyme Activity
4.4 Mechanisms of Crystallin Aging
4.5 Conclusions
5 Summation
Figure 1. Figure 1.

Age‐related change in the excretion of hydroxyproline in 5‐, 15‐, and 28‐month‐old Wistar rats.

From Mohan and Radha 414, by copyright permission from Academic Press
Figure 2. Figure 2.

Rates of collagen digestion vs. age for rat (○), dog (▴), macaque (♦), and human (•). NaOH required (μl as shown of a 0.01M solution) to maintain pH 7.8 at 37°C during the initial 35 min of collagenase digestion.

From Hamlin et al. 229 Copyright 1980, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK
Figure 3. Figure 3.

Relationship between tail tendon denaturation (measured by tendon breaking time) and age of B6 male mice.

From Harrison et al. 238, copyright permission from Taylor and Francis
Figure 4. Figure 4.

Effect of hypophysectomy (LEAN HYP 7) and hypophysectomy with hypothalamic lesions (FAT HYP 15) at age 70 days on the aging of tail tendon collagen measured by tendon breaking time in minutes. INTACT 19 refers to ad libitum fed rats eating 19 g of food per day. INTACT 15 and 7 refer to rats fed 15 and 7 g of food per day. The collagen aging rate (slope of the regression line) in hypophysectomized rats is slower than that in intact rats eating the same amount of food.

From Everitt et al. 152, copyright permission from Elsevier Scientific Publishers Ireland Ltd
Figure 5. Figure 5.

Age‐related changes in content of collagen cross‐links in human tooth tissue. Upper: dentin; DHLN, dehydrodihydroxylysinonorleucine; HLN, dehydrohydroxylysinonorleucine; HP, hydroxypyridinoline; LP, lysylpyridinoline. Lower: pulp. Line A (•) represents DHLNL; line B (□) represents HLNL; line C (○) represents LNL.

Upper from Walters and Eyre 678 by copyright permission from Springer‐Verlag, New York; Lower from Nielsen et al. 447 Copyright 1983, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK
Figure 6. Figure 6.

Age‐related changes in the nonreducible cross‐link pyridinoline of collagen. Upper: Medial (MCL) and anterior (ACL) cruciate ligament of rabbits. Middle: Contents in rat (A) costal cartilage and (B) Achilles tendon. Lower: Rat mandibular bone.

Upper from Amiel et al. 7 by copyright permission from The Gerontological Society of America; middle from Moriguchi and Fujimoto 432 by permission; Lower from Shikata et al. 576 Copyright 1985, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK
Figure 7. Figure 7.

Changes in the contents of cross‐linking amino acids of human aorta with age. A: Histidinoalanine (HISA), B: pyridinoline (PYR), C: desmosine (DES), and D: isodesmosine (IDE).

From Fujimoto 181, by copyright permission from Academic Press
Figure 8. Figure 8.

Age‐related changes in pyridinoline content of cartilage from human (A) costal cartilage and (B) Achilles tendon: ○, male; •, female.

From Moriguchi and Fujimoto 432, by permission
Figure 9. Figure 9.

Changes in the content of histidinohydroxylysinonorleucine with age in bovine (upper) and human (lower).

From Yamauchi et al. 688, by copyright permission from Academic Press
Figure 10. Figure 10.

Histidinoalanine content as a function of age. Upper: Human costal cartilage (○), Achilles tendon (□), aorta (Δ), and skin (•). Lower: Rat mandibular bone.

Upper from Fujimoto 182; by copyright permission from Academic Press. Lower from Shikata et al. 576 Copyright 1985, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK
Figure 11. Figure 11.

Scheme representing potential stages of the Maillard reaction (nonenzymatic browning) corresponding to initiation, propagation, and termination events, respectively.

From Monnier et al. 426, by permission
Figure 12. Figure 12.

Age‐dependent changes in glycation of human skin collagen measured by fructose‐lysine (FL) content (acid‐hydrolyzed product is furosine). Shaded area at the bottom includes 95% confidence limits for similar analyses of normal lens proteins.

Reprinted with permission from Dunn et al. 138. Copyright 1991, American Chemical Society
Figure 13. Figure 13.

Age‐dependent changes in the concentration of Nε‐CML in human skin collagen. A: Concentration of CML, normalized to the lysine content of collagen. Shaded area represents 95% confidence limits for similar analyses of normal lens proteins. B: Concentration of CML normalized to the fructose‐lysine (FL) content of collagen. Shaded area at top represents 95% confidence limits for similar analyses of normal lens proteins. Note that the slope for the lens data vs. age is approximately 20 times that observed for skin collagen.

Reprinted with permission from Dunn et al. 138. Copyright 1991, American Chemical Society
Figure 14. Figure 14.

Age‐related increase in fluorescence (excitation/emission at 370/440 nm) in human dura mater. Nondiabetic (•), type I diabetic (○), type II diabetic (Δ); 95% confidence limits for nondiabetic control subjects.

From Monnier et al. 425, by permission
Figure 15. Figure 15.

Age‐related changes of pentosidine in human dura mater and skin.

Upper from Sell and Monnier 569 by permission; Lower from Sell et al. 571, by permission
Figure 16. Figure 16.

Pentosidine and pyridinoline contents of human articular cartilage as a function of age.

From Uchiyama et al. 646, by permission
Figure 17. Figure 17.

Determination of AGE in aortic collagen of male Lewis rats with and without diabetes. Diabetes was induced in Lewis rats with either alloxan or streptozotocin at 8 wk of age. At 16 wk intervals, six animals were killed and the aortic collagen analyzed for hydroxyproline, fluorescence, and AGE content by ELISA. Values are expressed per mg of hydroxyproline. A: Relative fluorescence at excitation/emission 370/440 nm. B: Collagen‐bound AGEs measured by ELISA. ○, Control rats; ▴, rats with alloxan‐induced diabetes; ▾, rats with streptozotocin‐induced diabetes. Each value shown is the mean of six experimental animals.

From Makita et al. 379, by permission
Figure 18. Figure 18.

D‐Aspartate accumulation in human elastin as a function of age. Upper: Lung parenchymal elastin. Lower: Aorta. (▪) Elastin, (□) collagen, (Δ) elastin‐bound glycoprotein.

Upper from Shapiro et al. 575, by copyright permission of the American Society for Clinical Investigation. Lower from Powell et al. 496, by copyright permission from Portland Press Ltd., Colchester, UK
Figure 19. Figure 19.

Total uronic acid (as a measure of total proteoglycan estimate) and hyaluronic acid contents in papain digest of human articular cartilage.

From Holmes et al. 257, by copyright permission from Portland Press Ltd., Colchester, UK
Figure 20. Figure 20.

Changes in molecular weight of hyaluronic acid over human life span.

From Holmes et al. 257, by copyright permission from Portland Press Ltd., Colchester, UK
Figure 21. Figure 21.

Diagrammatic section of dog lens.

From van Heyningen, 657, by permission
Figure 22. Figure 22.

Separation by gel filtration of the water‐soluble lens proteins on an Ultrogel AcA 34 column.

From Bloemendal and Zweers 51, by permission
Figure 23. Figure 23.

Intensification of blue light absorption (at 440 nm) of noncataractous human lenses with increasing age. Points for the paired lenses of one individual are joined by a vertical line.

From Zigman 696, by permission
Figure 24. Figure 24.

Fluorescence intensity ratios of 360‐nm fluorogen (I 360/290) in normal aging lens (solid line), nuclear cataracts (heavy solid line), and percent insoluble protein in normal aging lens (dotted line) and nuclear cataracts (heavy dotted line).

From Lerman and Borkman 349, by permission
Figure 25. Figure 25.

Racemization of L‐aspartic acid expressed as D/L aspartic acid in human lens crystallins as a function of age.

From Masters et al. 389, by permission
Figure 26. Figure 26.

Schematic representation of lens membrane‐cytosol protein aggregates. A: Depiction of aggregates in the nuclear (inner) region of the lens. Intrinsic and extrinsic membrane proteins are disulfide‐linked to cytosol protein units, which are in turn disulfide‐linked to each other. Such giant aggregates scatter light and contribute to the loss of transparency. B: Aggregates in the outer cortical region of the lens. While nuclear fiber cell membranes appear to be rigid and do not break with aggregate formation, in the cortical region the formation of the aggregates causes membrane to rupture and the appearance of the membrane fragments linked to cytosol protein, as well as the nuclear region type of aggregate.

From Spector 594, by copyright permission from Academic Press
Figure 27. Figure 27.

Structures of postsynthetic modifications of amino acid residues in aging human lens. A: Cysteine disulfide, B: methionine sulfoxide, C: methionine sulfone, D: lanthionine, E: histidinoalanine, F: γ‐ glutamyllysine, G: dityrosine, H: ε‐fructosyllysine, I: Heyns rearrangement of fructose lysine adduct, J: carboxymethyllysine, K: pentosidine, L: kynurenine, M: β‐carboline, N: anthranilic acid.
Figure 28. Figure 28.

Hypothetical mechanisms of protection against damage to lens crystallins by the ascorbate‐mediated advanced Maillard reaction.
Figure 29. Figure 29.

Pentosidine levels in cataractous lenses classified on the basis of pigmentation. Results are expressed as the mean ± SD. Statistical significance was calculated using Student's nonpaired t test. *Significantly different compared to normal lenses (P < 0.005). Nor, normal; Ty, type; Brun, brunescent; Diab, diabetic.

From Nagaraj et al. 439, by permission


Figure 1.

Age‐related change in the excretion of hydroxyproline in 5‐, 15‐, and 28‐month‐old Wistar rats.

From Mohan and Radha 414, by copyright permission from Academic Press


Figure 2.

Rates of collagen digestion vs. age for rat (○), dog (▴), macaque (♦), and human (•). NaOH required (μl as shown of a 0.01M solution) to maintain pH 7.8 at 37°C during the initial 35 min of collagenase digestion.

From Hamlin et al. 229 Copyright 1980, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK


Figure 3.

Relationship between tail tendon denaturation (measured by tendon breaking time) and age of B6 male mice.

From Harrison et al. 238, copyright permission from Taylor and Francis


Figure 4.

Effect of hypophysectomy (LEAN HYP 7) and hypophysectomy with hypothalamic lesions (FAT HYP 15) at age 70 days on the aging of tail tendon collagen measured by tendon breaking time in minutes. INTACT 19 refers to ad libitum fed rats eating 19 g of food per day. INTACT 15 and 7 refer to rats fed 15 and 7 g of food per day. The collagen aging rate (slope of the regression line) in hypophysectomized rats is slower than that in intact rats eating the same amount of food.

From Everitt et al. 152, copyright permission from Elsevier Scientific Publishers Ireland Ltd


Figure 5.

Age‐related changes in content of collagen cross‐links in human tooth tissue. Upper: dentin; DHLN, dehydrodihydroxylysinonorleucine; HLN, dehydrohydroxylysinonorleucine; HP, hydroxypyridinoline; LP, lysylpyridinoline. Lower: pulp. Line A (•) represents DHLNL; line B (□) represents HLNL; line C (○) represents LNL.

Upper from Walters and Eyre 678 by copyright permission from Springer‐Verlag, New York; Lower from Nielsen et al. 447 Copyright 1983, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK


Figure 6.

Age‐related changes in the nonreducible cross‐link pyridinoline of collagen. Upper: Medial (MCL) and anterior (ACL) cruciate ligament of rabbits. Middle: Contents in rat (A) costal cartilage and (B) Achilles tendon. Lower: Rat mandibular bone.

Upper from Amiel et al. 7 by copyright permission from The Gerontological Society of America; middle from Moriguchi and Fujimoto 432 by permission; Lower from Shikata et al. 576 Copyright 1985, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK


Figure 7.

Changes in the contents of cross‐linking amino acids of human aorta with age. A: Histidinoalanine (HISA), B: pyridinoline (PYR), C: desmosine (DES), and D: isodesmosine (IDE).

From Fujimoto 181, by copyright permission from Academic Press


Figure 8.

Age‐related changes in pyridinoline content of cartilage from human (A) costal cartilage and (B) Achilles tendon: ○, male; •, female.

From Moriguchi and Fujimoto 432, by permission


Figure 9.

Changes in the content of histidinohydroxylysinonorleucine with age in bovine (upper) and human (lower).

From Yamauchi et al. 688, by copyright permission from Academic Press


Figure 10.

Histidinoalanine content as a function of age. Upper: Human costal cartilage (○), Achilles tendon (□), aorta (Δ), and skin (•). Lower: Rat mandibular bone.

Upper from Fujimoto 182; by copyright permission from Academic Press. Lower from Shikata et al. 576 Copyright 1985, with kind permission from Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK


Figure 11.

Scheme representing potential stages of the Maillard reaction (nonenzymatic browning) corresponding to initiation, propagation, and termination events, respectively.

From Monnier et al. 426, by permission


Figure 12.

Age‐dependent changes in glycation of human skin collagen measured by fructose‐lysine (FL) content (acid‐hydrolyzed product is furosine). Shaded area at the bottom includes 95% confidence limits for similar analyses of normal lens proteins.

Reprinted with permission from Dunn et al. 138. Copyright 1991, American Chemical Society


Figure 13.

Age‐dependent changes in the concentration of Nε‐CML in human skin collagen. A: Concentration of CML, normalized to the lysine content of collagen. Shaded area represents 95% confidence limits for similar analyses of normal lens proteins. B: Concentration of CML normalized to the fructose‐lysine (FL) content of collagen. Shaded area at top represents 95% confidence limits for similar analyses of normal lens proteins. Note that the slope for the lens data vs. age is approximately 20 times that observed for skin collagen.

Reprinted with permission from Dunn et al. 138. Copyright 1991, American Chemical Society


Figure 14.

Age‐related increase in fluorescence (excitation/emission at 370/440 nm) in human dura mater. Nondiabetic (•), type I diabetic (○), type II diabetic (Δ); 95% confidence limits for nondiabetic control subjects.

From Monnier et al. 425, by permission


Figure 15.

Age‐related changes of pentosidine in human dura mater and skin.

Upper from Sell and Monnier 569 by permission; Lower from Sell et al. 571, by permission


Figure 16.

Pentosidine and pyridinoline contents of human articular cartilage as a function of age.

From Uchiyama et al. 646, by permission


Figure 17.

Determination of AGE in aortic collagen of male Lewis rats with and without diabetes. Diabetes was induced in Lewis rats with either alloxan or streptozotocin at 8 wk of age. At 16 wk intervals, six animals were killed and the aortic collagen analyzed for hydroxyproline, fluorescence, and AGE content by ELISA. Values are expressed per mg of hydroxyproline. A: Relative fluorescence at excitation/emission 370/440 nm. B: Collagen‐bound AGEs measured by ELISA. ○, Control rats; ▴, rats with alloxan‐induced diabetes; ▾, rats with streptozotocin‐induced diabetes. Each value shown is the mean of six experimental animals.

From Makita et al. 379, by permission


Figure 18.

D‐Aspartate accumulation in human elastin as a function of age. Upper: Lung parenchymal elastin. Lower: Aorta. (▪) Elastin, (□) collagen, (Δ) elastin‐bound glycoprotein.

Upper from Shapiro et al. 575, by copyright permission of the American Society for Clinical Investigation. Lower from Powell et al. 496, by copyright permission from Portland Press Ltd., Colchester, UK


Figure 19.

Total uronic acid (as a measure of total proteoglycan estimate) and hyaluronic acid contents in papain digest of human articular cartilage.

From Holmes et al. 257, by copyright permission from Portland Press Ltd., Colchester, UK


Figure 20.

Changes in molecular weight of hyaluronic acid over human life span.

From Holmes et al. 257, by copyright permission from Portland Press Ltd., Colchester, UK


Figure 21.

Diagrammatic section of dog lens.

From van Heyningen, 657, by permission


Figure 22.

Separation by gel filtration of the water‐soluble lens proteins on an Ultrogel AcA 34 column.

From Bloemendal and Zweers 51, by permission


Figure 23.

Intensification of blue light absorption (at 440 nm) of noncataractous human lenses with increasing age. Points for the paired lenses of one individual are joined by a vertical line.

From Zigman 696, by permission


Figure 24.

Fluorescence intensity ratios of 360‐nm fluorogen (I 360/290) in normal aging lens (solid line), nuclear cataracts (heavy solid line), and percent insoluble protein in normal aging lens (dotted line) and nuclear cataracts (heavy dotted line).

From Lerman and Borkman 349, by permission


Figure 25.

Racemization of L‐aspartic acid expressed as D/L aspartic acid in human lens crystallins as a function of age.

From Masters et al. 389, by permission


Figure 26.

Schematic representation of lens membrane‐cytosol protein aggregates. A: Depiction of aggregates in the nuclear (inner) region of the lens. Intrinsic and extrinsic membrane proteins are disulfide‐linked to cytosol protein units, which are in turn disulfide‐linked to each other. Such giant aggregates scatter light and contribute to the loss of transparency. B: Aggregates in the outer cortical region of the lens. While nuclear fiber cell membranes appear to be rigid and do not break with aggregate formation, in the cortical region the formation of the aggregates causes membrane to rupture and the appearance of the membrane fragments linked to cytosol protein, as well as the nuclear region type of aggregate.

From Spector 594, by copyright permission from Academic Press


Figure 27.

Structures of postsynthetic modifications of amino acid residues in aging human lens. A: Cysteine disulfide, B: methionine sulfoxide, C: methionine sulfone, D: lanthionine, E: histidinoalanine, F: γ‐ glutamyllysine, G: dityrosine, H: ε‐fructosyllysine, I: Heyns rearrangement of fructose lysine adduct, J: carboxymethyllysine, K: pentosidine, L: kynurenine, M: β‐carboline, N: anthranilic acid.



Figure 28.

Hypothetical mechanisms of protection against damage to lens crystallins by the ascorbate‐mediated advanced Maillard reaction.



Figure 29.

Pentosidine levels in cataractous lenses classified on the basis of pigmentation. Results are expressed as the mean ± SD. Statistical significance was calculated using Student's nonpaired t test. *Significantly different compared to normal lenses (P < 0.005). Nor, normal; Ty, type; Brun, brunescent; Diab, diabetic.

From Nagaraj et al. 439, by permission
References
 1. Adams, P., and H. Mum. Qualitative changes with age of proteoglycans of human lumbar discs. Ann. Rheum. Dis. 35: 289–296, 1976.
 2. Ahmed, M. U., J. A. Dunn, M. D. Walla, S. R. Thorpe, and J. W. Baynes. Oxidative degradation of glucose adducts to protein: formation of 3‐(Nε‐lysino)‐lactic acid from model compounds and glycated proteins. J. Biol. Chem. 263: 8816–8821, 1988.
 3. Ahmed, M. U., S. R. Thorpe, and J. W. Baynes. Identification of Nε‐carboxymethyllysine as a degradation product of fructo‐selysine in glycated protein. J. Biol. Chem. 261: 4889–4894, 1986.
 4. Albini, A., B. Pontz, M. Pulz, G. Allavena, H. Mensing, and P. K. Müller. Decline of fibroblast chemotaxis with age of donor and cell passage number. Coll. Relat. Res. 8: 23–37, 1988.
 5. Alnaqeeb, M. A., N. S. Al Zaid, and G. Goldspink. Connective tissue changes and physical properties of developing and ageing skeletal muscle. J. Anat. 139: 677–689, 1984.
 6. Amici, A., R. L. Levine, L. Tsai, and E. R. Stadtman. Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal catalyzed oxidation reactions. J. Biol. Chem. 264: 3341–3346, 1989.
 7. Amiel, D., S. D. Kuiper, C. D. Wallace, F. L. Harwood, and J. S. Vandeberg. Age‐related properties of medial collateral ligament: a morphologic and collagen maturation study in the rabbit. J. Gerontol. 46: B159–B165, 1991.
 8. Anderson, E., and A. Spector. The state of sulfhydryl groups in normal and cataracous lens proteins. I. Nuclear region. Exp. Eye Res. 26: 407–417, 1978.
 9. Anderson, E. I., D. D. Wright, and A. Spector. The state of sulfhydryl groups in normal and cataractous human lens proteins. II. Cortical and nuclear regions. Exp. Eye Res. 29: 233–243, 1978.
 10. Andley, U. Spectroscopic studies on the riboflavin‐sensitized conformational changes of calf lens α‐crystallin. Exp. Eye Res. 46: 531–544, 1988.
 11. Andreotti, L., A. Bussotti, D. Cammelli, E. Aiello, and S. Sampognaro. Connective tissue in aging lung. Gerontology 29: 377–387, 1983.
 12. Andreotti, L., D. Camelli, A. Bussotti, and P. Arcangeli. Biochemical measurement of lung connective tissue. Bull. Eur. Physiopathol. Respir. 16: 83–90, 1980.
 13. Angyal, S. J. The composition of reducing sugars in solution. Adv. Carbohydr. Chem. Biochem. 42: 15–68, 1984.
 14. Ansari, N. H., and S. K. Srivastava. Role of glutathione in the prevention of cataractogenesis in rat lenses. Curr. Eye Res. 2: 271–275, 1982–1983.
 15. Anversa, P., T. Palackal, E. H. Sonnenblick, G. Olivetti, L. G. Meggs, and J. M. Capasso. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ. Res. 67: 871–885, 1990.
 16. Araki, N., N. Ueno, B. Chakrabarti, Y. Morino, and S. Horiuchi. Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. J. Biol. Chem. 267: 10211–10214, 1992.
 17. Asghar, A., and R. L. Henrickson. Chemical, biochemical, functional and nutritional characteristics of collagen in food systems. Adv. Food Res. 28: 231–372, 1982.
 18. Augusteyn, R. C. Human lens albuminoid. Jpn. J. Ophthalmol. 18: 127–134, 1974.
 19. Augusteyn, R. C. Distribution of fluorescence in the human cataractous lens. Ophthalmic Res. 7: 217–224, 1975.
 20. Augusteyn, R. C., Protein modification in cataract: possible oxidative mechanism. In: Mechanisms of Cataract Formation in Human Lens, edited by G. Duncan. New York: Academic Press, 1981, p. 72–115.
 21. Auricchio, G., and M. Testa. Some biochemical differences between cortical (pale) and nuclear (brown) cataracts. Ophthalmologica 164: 228–235, 1972.
 22. Ayisi, K., J. Lindner, J. Krohn, and I. Mangold. Investigations on connective tissue metabolism: ageing of the human heart. Mech. Ageing Dev. 14: 325–331, 1980.
 23. Bailey, A. J., and C. M. Peach. Isolation and structural identification of a labile intermolecular crosslink in collagen. Biochem. Biophys. Res. Commun. 33: 812–189, 1968.
 24. Baker, G. T., III, and R. L. Sprott. Biomarkers of aging. Exp. Gerontol. 23: 223–239, 1988.
 25. Barber, G. W., Biochemistry of cataracts. In: Pathobiology of Ocular Disease, edited by A. Garner and G. K. Klintworth. New York: Marcel Dekker, 1982, p. 1273–1302.
 26. Barber, M., R. S. Bordoli, G. J. Elliott, D. Fujimoto, and J. E. Scott. The structure(s) of pyridinoline(s). Biochem. Biophys. Res. Commun. 109: 1041–1046, 1982.
 27. Barber, W. C. Human cataractogenesis: a review. Exp. Eye Res. 16: 985–991, 1973.
 28. Barnard, K., N. D. Light, T. J. Sims, and A. J. Bailey. Chemistry of the collagen crosslinks: origin and partial characterization of a putative mature crosslink of collagen. Biochem. J. 244: 303–309, 1987.
 29. Barnes, M. J., B. J. Constable, L. F. Morton, and P. M. Royce. Age‐related variations in hydroxylation of lysine and proline in collagen. Biochem. J. 139: 461–468, 1974.
 30. Bartold, P. M., R. R. Boyd, and R. C. Page. Proteoglycans synthesized by gingival fibroblasts derived from human donors of different ages. J. Cell Physiol. 126: 37–46, 1986.
 31. Bayliss, M. T., Proteoglycan structure in normal and osteoarthritic human cartilage. In: Articular Cartilage Biochemistry, edited by K. E. Kuettner, R. Schleyerbach, and V. C. Hascall. New York: Raven Press, 1986, p. 295–310.
 32. Bayliss, M. T. Proteoglycan structure and metabolism during maturation and ageing of human articular cartilage. Biochem. Soc. Trans. 18: 799–802, 1990.
 33. Baynes, J. W. Role of oxidative stress in development of complications in diabetes. Diabetes 40: 405–412, 1991.
 34. Baynes, J. W., N. G. Watkins, C. I. Fisher, C. J. Hull, J. S. Patrick, M. U. Ahmed, J. A. Dunn, and S. R. Thorpe. The Amadori product on protein: structure and reactions. In: The Maillard Reaction in Aging, Diabetes, and Nutrition, edited by J. W. Baynes and V. M. Monnier. New York: Alan R. Liss, 1989, p. 43–67.
 35. Benedek, G. B. Theory of transparency of the eye. Appl. Optics 10: 459–473, 1971.
 36. Benjamin, M., R. N. S. Tyers, and J. R. Ralphs. Age‐related changes in tendon fibrocartilage. J. Anat. 179: 127–136, 1991.
 37. Bensch, K. G., J. E. Fleming, and W. Lohman. The role of ascorbic acid in senile cataract. Proc. Natl. Acad. Sci. USA 82: 7193–7196, 1985.
 38. Bernick, S., and R. Cailliet. Vertebral end‐plate changes with aging of human vertebrae. Spine 7: 97–102, 1982.
 39. Bessems, G. J. H., B. M. Deman, J. Bours, and H. J. Hoenders. Age‐related variations in the distribution of crystallins within the bovine lens. Exp. Eye Res. 43: 1019–1030, 1986.
 40. Bessems, G. J. H., H. J. J. M. Rennen, and H. J. Hoenders. Lanthionine, a protein crosslink in cataractous human lenses. Exp. Eye Res. 44: 691–695, 1987.
 41. Beswick, H. T., and J. J. Harding. Conformational changes induced in the α‐ and γ‐crystallins by modification with glucose 6‐phosphate. Biochem. J. 246: 761–769, 1987.
 42. Betsch, D. F., and E. Baer. Structure and mechanical properties of rat tail tendon. Biorheology 17: 83–94, 1980.
 43. Bhuyan, K. C., and D. K. Bhuyan. Regulation of hydrogen peroxide in eye humors. Effect of 3‐amino‐1H‐1,2,4‐triazole on catalase and GSH peroxidase in rabbit eye. Biochim. Biophys. Acta 497: 641–651, 1977.
 44. Bhuyan, K. C., and D. K. Bhuyan. Mechanism of cataractogenesis induced by 3‐aminotriazole. I. Morphology and histopathology of cataract and the role of catalase in the regulation of H2 O2 in the eye. In: Biochemical and Clinical Aspects of Oxygen, edited by W. S. Caughey. New York: Academic Press, 1979, p. 789–796.
 45. Bienkowski, R. S., B. J. Baum, and R. G. Crystal. Fibroblasts degrade newly synthesized collagen within the cell before secretion. Nature 276: 413–416, 1978.
 46. Bienkowski, R. S., M. J. Cowan, J. A. McDonald, and R. G. Crystal. Degradation of newly synthesized collagen. J. Biol. Chem. 253: 4356–4363, 1978.
 47. Bihari‐Varga, M., E. Csonka, E. Gruber, and H. Jellinek. Age‐related changes in the glycosaminoglycans and collagen of cultured pig endothelial cells. Pathol. Biol. (Paris) 29: 555561, 1981.
 48. Björksten, J., and W. J. Champion. Mechanical influence upon tanning. J. Am. Chem. Soc. 64: 868–869, 1942.
 49. Blackett, A. D., and D. A. Hall. Vitamin E—its significance in mouse ageing. Age Ageing 10: 191–195, 1981.
 50. Bleeker, J. C., J. A. Van Best, L. Vrij, and E. A. van der Velde. Autofluorescence of the lens in diabetic and healthy subjects by fluorometry. Invest. Ophthalmol. Vis. Sci. 27: 791–794, 1986.
 51. Bloemendal, H., and A. Zweers. Improved separation of low molecular weight crystallins. In: Progress of Lens Biochemistry Research, edited by Doc. Ophthalmol. (The Hague) 15: 91104, 1976.
 52. Blomfield, J., and J. F. Farrar. Fluorescence spectra of arterial elastin. Biochem. Biophys. Res. Commun. 28: 346–351, 1967.
 53. Blomfield, J., and J. F. Farrar. The fluorescent properties of maturing arterial elastin. Cardiovasc. Res. 3: 161–170, 1969.
 54. Bochantin, J., and L. L. Mays. Age‐dependence of collagen tail fiber breaking strength in Sprague‐Dawley and Fischer 344 rats. Exp. Gerontol. 16: 101–106, 1981.
 55. Borchman, D., C. A. Paterson, and N. A. Delamere. Oxidative inhibition of Ca2+‐ATPase in the rabbit lens. Invest. Ophthalmol. Vis. Sci. 30: 1633–1637, 1989.
 56. Borg, T. K., and J. B. Caulfield. The collagen matrix of the heart. Fed. Proc. 40: 2037–2041, 1981.
 57. Bouissou, H., and T. Pieraggi. Changes in the morphology and chemistry of connective tissues during aging. In: Collagen, edited by M. E. Nimni. Boca Raton, FL: CRC Press, 1988, vol. II, p. 95–111.
 58. Bouissou, H., T. Pieraggi, M. Julian, and L. Douste‐Blazy. Cutaneous aging. Its relation with arteriosclerosis and atheroma. In: Frontiers of Matrix Biology, edited by L. Robert. New York: Karger, 1973, vol. I, p. 190–211.
 59. Bouissou, H., T. Pieraggi, M. Julian, and L. Douste‐Blazy. Simultaneous degradation of elastin in dermis and in aorta. In: Frontiers of Matrix Biology, edited by L. Robert. New York: Karger, 1976, vol. III, p. 242–255.
 60. Boyer, B., P. Kern, A. Fourtanier, and J. Labat‐Robert. Age‐dependent variations of the biosynthesis of fibronectin and fibrous collagens in mouse skin. Exp. Gerontol. 26: 375–383, 1991.
 61. Bradley, K. H., S. D. McConnell, and R. G. Crystal. Lung collagen composition and synthesis. J. Biol. Chem. 244: 2674–2683, 1974.
 62. Brand, H. S., M. H. M. T. de Koning, G. P. J. van Kampen, and J. K. van der Korst. Age‐related changes in the turnover of proteoglycans from explants of bovine articular cartilage. J. Rheumatol. 18: 599–605, 1991.
 63. Brandt, K. D., and R. S. Fife. Ageing in relation to the pathogenesis of osteoarthritis. Clin. Rheum. Dis. 12: 117–130, 1986.
 64. Braverman, I. M., and E. Fonferko. Studies in cutaneous aging: I. The elastic fiber network. J. Invest. Dermatol. 78: 434–443, 1982.
 65. Braverman, I. M., and A. Keh‐Yen. Ultrastructural abnormalities of the microvasculature and elastic fibers in the skin of juvenile diabetics. J. Invest. Dermatol. 82: 270–274, 1984.
 66. Brody, J. S., H. Kagan, and A. Manalo. Lung lysyl oxidase activity: relation to lung growth. Am. Rev. Respir. Dis. 120: 1289–1295, 1979.
 67. Brownlee, M., A. Cerami, and H. Vlassara. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N. Engl. J. Med. 318: 1315–1321, 1988.
 68. Brownlee, M., S. Pongor, and A. Cerami. Covalent attachment of soluble proteins by nonenzymatically glycosylated collagen. J. Exp. Med. 158: 1739–1744, 1983.
 69. Brunk, U. T., C. B. Jones, and R. S. Sohal. A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis. Mutat. Res. 275: 395–403, 1992.
 70. Buckingham, R. H. The behavior of reduced proteins from normal and cataractous lenses in highly dissociating media: cross‐linked protein in cataractous lenses. Exp. Eye Res. 14: 123–129, 1972.
 71. Buddecke, E., and M. Sziegoleit. Isolierung, chemische zusammensetzung und altersabhangige verteilung von mucopolysaccharinden menschlicher zwischenwirbelscheiben. Hoppe Seyler Physiol. Chem. 337: 66–78, 1964.
 72. Bunn, H. F. Non‐enzymatic glycosylation of protein: a form of molecular aging. Schweiz. Med. Wochenschr. III: 1503–1507, 1981.
 73. Bunn, H. F., and P. J. Higgins. Reaction of monosaccharides with proteins: possible evolutionary significance. Science 213: 222–224, 1981.
 74. Calkins, E. Aging of cells and people. Clin. Obstet. Gynecol. 24: 165–179, 1981.
 75. Calvin, H. I., C. Medvedovski, J. C. David, T. M. Broglio, J. L. Hess, S. C. J. Fu, and B. V. Worgul. Rapid deterioration of lens fibers in GHS‐depleted mouse pups. Invest. Ophthalmol. Vis. Sci. 32: 1916–1924, 1991.
 76. Campbell, M. A., C. J. Handley, V. C. Hascall, R. A. Campbell, and D. A. Lowther. Turnover of proteoglycans in cultures of bovine articular cartilage. Arch. Biochem. Biophys. 234: 275–289, 1984.
 77. Caplan, A. Cartilage Sci. Am. 251: 84–94, October 1984.
 78. Cappelli, V., R. Forni, C. Poggesi, C. Reggiani, and L. Ricciardi. Age‐dependent variations of diastolic stiffness and collagen content in rat ventricular myocardium. Arch. Int. Physiol. Biochem. 92: 93–106, 1984.
 79. Carney, S. L., and H. Muir. The structure and function of cartilage proteoglycans. Physiol. Rev. 68: 858–910, 1988.
 80. Casarett, G. W., Acceleration of aging by ionizing radiations. In: The Biology of Aging, edited by B. Strehler. Washington D.C.: Institute of Biological Sciences, 1960, p. 147–152.
 81. Castelo‐Branco, C., M. Duran, and J. González‐Merlo. Skin collagen changes related to age and hormone replacement therapy. Maturitas 15: 113–119, 1992.
 82. Castillo, Y., H. Kruger, J. Arais‐Stella, A. Hurtado, P. Harris, and D. Heath. Histology, extensibility, and chemical composition of pulmonary trunk in persons living at sea level and at high altitude in Peru. Br. Heart J. 29: 120–128, 1967.
 83. Cerami, A. Hypothesis: glucose as a mediator of aging. J. Am. Geriatr. Soc. 33: 626–634, 1985.
 84. Cerami, A., H. Vlassara, and M. Brownlee. Glucose and aging. Sci. Am. 257: 90–96, May 1987.
 85. Cetta, G., R. Tenni, G. Zanaboni, G. Deluca, E. Ippolito, C. De Martino and A. A. Castellani. Biochemical and morphological modifications in rabbit Achilles tendon during maturation and ageing. Biochem. J. 204: 61–67, 1982.
 86. Chang, J. C. F., P. C. Ulrich, R. Bucala, and A. Cerami. Detection of an advanced glycosylation product bound to protein in situ. J. Biol. Chem. 260: 7970–7974, 1985.
 87. Charlton, J. M., and R. Van Heyningen. Glucose 6‐phosphate dehydrogenase in the mammalian lens. Exp. Eye Res. 11: 351–355, 1971.
 88. Chase, K. V., R. Carubelli, and R. E. Nordquist. The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates. Arch. Biochem. Biophys. 288: 473–480, 1991.
 89. Cheng, H. M., and L. T. Chylack. Lens metabolism. In: The Ocular Lens, edited by H. Maisel. New York: Marcel Dekker, 1985, p. 223–264.
 90. Cheng, R.‐Z., J. Tsunehiro, K. Uchida, and S. Kawakishi. Oxidative damage of glycated protein in the presence of transition metabolism. Agric. Biol. Chem. 55: 1993–1988, 1991.
 91. Chio, K. S., and A. L. Tappel. Synthesis and characterization of the fluorescent products derived from malonaldehyde and amino acids. Biochemistry 8: 2821–2827, 1969.
 92. Chio, K. S., and A. L. Tappel. Inactivation of ribonuclease and other enzymes by peroxidizing lipids and by malonaldehyde. Biochemistry 8: 2827–2832, 1969.
 93. Chio, K. S., U. Reiss, B. Fletcher, and A. L. Tappel. Peroxidation of subcellular organelles: formation of lipofuscinlike fluorescent pigments. Science 166: 1535–1536, 1969.
 94. Chiou, S. H., L. T. Chylack, H. F. Bunn, and J. H. Kinoshita. Role of nonenzymatic glycosylation in experimental cataract formation. Biochem. Biophys. Res. Comm. 95: 894–890, 1980.
 95. Chiou, S. H., L. T. Chylack, W. H. Tung, and H. F. Bunn. Nonenzymatic glycosylation of bovine lens crystallins. J. Biol. Chem. 256: 5176–5180, 1981.
 96. Chobanian, A. V., M. F. Prescott, and C. C. Haudenschild. Recent advances in molecular pathology: the effects of hypertension on the arterial wall. Exp. Mol. Pathol. 41: 153–169, 1984.
 97. Choi, A. M. K., D. R. Olsen, K. G. Cook, S. F. Deamond, J. Uitto, and S. A. Bruce. Differential extracellular matrix gene expression by fibroblasts during their proliferative life span in vitro and at senescence. J. Cell. Physiol. 151: 147–155, 1992.
 98. Clark, H. M., S. Zigman, and S. Lerman. Studies on the structural proteins of the human lens. Exp. Eye Res. 8: 172–182, 1969.
 99. Cleary, E. G., The microfibrillar component of the elastic fibers. Morphology and biochemistry. In: Connective Tissue Disease: Molecular Pathology of the Extracellular Matrix, edited by J. Uitto and A. J. Perejda. New York: Marcel Dekker, 1987, p. 55–81.
 100. Cliff, W. J. The aortic tunica media in aging rats. Exp. Mol. Pathol. 13: 172–189, 1970.
 101. Coghlan, S. D., and R. C. Augusteyn. Changes in the distribution of proteins in the aging human lens. Exp. Eye Res. 25: 603–611, 1977.
 102. Cohen, M. P., and L. Ku. Age‐related changes in sulfation of basement membrane glycosaminoglycans. Exp. Gerontol. 18: 447–450, 1983.
 103. Cohen, M. P., and V. Yu‐Wu. Age‐related change in non‐enzymatic glycosylation of human basement membranes. Exp. Gerontol. 18: 461–469, 1983.
 104. Cole, T. C., P. Ghosh, and T. K. F. Taylor. Variations of the proteoglycans of the canine intervertebral disc with ageing. Biochim. Biophys. Acta 880: 209–219, 1986.
 105. Cooper, B., J. M. Creeth, and A. S. R. Donald. Studies of the limited degradation of mucus glycoproteins. Biochem. J. 228: 615–626, 1985.
 106. Cornwell, G. G., III, B. P. Thomas, and D. L. Snyder. Myocardial fibrosis in aging germ‐free and conventional Lobund‐Wistar rats: the protective effect of diet restriction. J. Gerontol. 46: B167–B170, 1991.
 107. Craighead, J. E. Editorial: Is advanced basement membrane glycosyaltion reversible? Lab. Invest. 60: 471–472, 1989.
 108. Cronlund, A. L., and H. M. Kagan. Comparison of lysyl oxidase from bovine lung and aorta. Connect. Tissue Res. 15: 173–185, 1986.
 109. Danielsen, C. C. Thermal stability of reconstituted collagen fibrils. Shrinkage characteristics upon in vitro maturation. Mech. Ageing Dev. 15: 269–278, 1981.
 110. Danielsen, C. C. Mechanical properties of native and reconstituted rat tail tendon collagen upon maturation in vitro. Mech. Ageing Dev. 40: 9–16, 1987.
 111. Danielsen, C. C. Age‐related thermal stability and susceptibility to proteolysis of rat bone collagen. Biochem. J. 272: 697–701, 1990.
 112. Danielsen, C. C., T. T. Andreassen, and L. Mosekilde. Mechanical properties of collagen from decalcified rat femur in relation to age and in vitro maturation. Calcif. Tissue Int. 39: 69–73, 1986.
 113. Danielsen, C. C., L. Mosekilde, and T. T. Andreassen. Long‐term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties. Calcif. Tissue Int. 50: 169–174, 1992.
 114. Davidkova, E., and I. Svadlenka. Interactions of malonaldehyde with collagen. IV. Localisation of malonaldehyde binding site in collagen molecule. Lebensm. Unters. Forsch. 158: 279–283, 1975.
 115. Davison, P. F. The contribution of labile crosslinks to the tensile behavior of tendons. Connect. Tissue Res. 18: 293–305, 1989.
 116. de Mignard, V. A., and S. Bernick. Microvascular changes in aging human osseous tissue [Abstract]. Microvasc. Res. 17: S11, 1979.
 117. D'Errico, A., P. Scarani, E. Colosimo, M. Spina, W. F. Grigioni, and A. M. Mancini. Changes in the alveolar connective tissue of the ageing lung: an immunohistochemical study. Virchows Archiv [A]. 415: 137–144, 1989.
 118. Deyl, Z., G. M. Butenko, J. Hausmann, M. Horakova, and K. Macek. Increased glycation and pigmentation of collagen in aged and young parabiotic rats and mice. Mech. Ageing Dev. 55: 39–47, 1990.
 119. Deyl, Z., M. Horakova, and O. Vancikova. Changes in pyridinoline content of elastin during ontogeny. Mech. Ageing Dev. 17: 321–325, 1981.
 120. Deyl, Z., H. Sulcova, R. Praus, and J. N. Goldman. A fluorescent compound in collagen and its relation to the age of the animal. Exp. Gerontol. 5: 57–62, 1970.
 121. Dickson, I. R., and M. K. Bagga. Changes with age in the non‐collagenous proteins of human bone. Connect. Tissue Res. 14: 77–85, 1985.
 122. Dilley, K. J. Ultraviolet light and human cataract [Letter]. Nature 257: 71, 1975.
 123. Dilley, K. J., and A. Pirie. Changes to the proteins of human lens nucleus in cataract. Exp. Eye Res. 19: 59–72, 1974.
 124. Dillon, J. Photolytic changes in lens proteins. Curr. Eye Res. 3: 145–150, 1984.
 125. Dillon, J., M. Garner, D. Roy, and A. Spector. The photolysis of lens protein: molecular changes. Exp. Eye Res. 34: 651–658, 1982.
 126. Dillon, J., A. Spector, and K. Nakanishi. Identification of β‐carbolines isolated from fluorescent human lens proteins. Nature 259: 471–483, 1976.
 127. Dische, Z. and H. Zil. Studies on the oxidation of cysteine to cystine in lens proteins during cataract formation. Am. J. Ophthalmol. 34: 104–113, 1951.
 128. Dische, Z., E. Borenfreund, and G. Zelmenis. Changes in lens proteins of rats during aging. Arch. Ophthalmol. 55: 471–483, 1956.
 129. Doege, K. J., M. Sasaki, E. Horigan, J. R. Hassell, and Y. Yamada. Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA clones. J. Biol. Chem. 262: 17757–17767, 1987.
 130. Doege, K. J., M. Sasaki, T. Kimura, and Y. Yamada. Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. J. Biol. Chem. 266: 894–902, 1991.
 131. Dovrat, A., and D. Gershon. Rat lens superoxide dismutase and glucose 6‐phosphate dehydrogenase: studies on the catalytic activity and fate of antigen as a function of age. Exp. Eye Res. 33: 651–661, 1981.
 132. Duance, V. C., and S. F. Wotton. Changes in the distribution of mammalian cartilage collagens with age. Biochem. Soc. Trans. 19: 376S, 1991.
 133. Dubick, M. A., R. B. Rucker, C. E. Cross, and J. A. Last. Elastin metabolism in rodent lung. Biochim. Biophys. Acta 672: 303–306, 1981.
 134. Dubina, T. L., V. A. Dyundikova, and E. V. Zhuk. Biological age and its estimation. II. Assessment of biological age of albino rats by multiple regression analysis. Exp. Gerontol. 18: 5–18, 1983.
 135. Dudhia, J., and T. E. Hardingham. The primary structure of human cartilage link protein. Nucleic Acids Res. 18: 1292, 1990.
 136. Duessen, A., and H. Pau. Nucleotide levels in human lens: regional distribution in different forms of senile cataract. Exp. Eye Res. 48: 37–47, 1989.
 137. Dunn, J. A., M. U. Ahmed, M. H. Murtiashaw, J. M. Richardson, M. D. Walla, S. R. Thorpe, and J. W. Baynes. Reaction of ascorbate with lysine and protein under oxidizing conditions. Formation of N‐(carboxymethyl)‐lysine by reaction between lysine products of autooxidation of ascorbate. Biochemistry 29: 10964–10970, 1990.
 138. Dunn, J. A., D. R. McCance, S. R. Thorpe, T. J. Lyons, and J. W. Baynes. Age‐dependent accumulation of N ε‐(carboxymethyl)lysine and N ε‐(carboxymethyl)‐hydroxylysinein human skin collagen. Biochemistry 30: 1205–1210, 1991.
 139. Dunn, J. A., J. S. Patrick, S. R. Thorpe, and J. W. Baynes. Oxidation of glycated proteins. Age‐dependent accumulation of Nε‐(carboxymethyl) lysine in lens proteins. Biochemistry 28: 9464–9468, 1990.
 140. Dyer, D. G., J. A. Blackledge, S. R. Thorpe, and J. W. Baynes. Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J. Biol. Chem. 266: 11654–11660, 1991.
 141. Dyundikova, V. A., Z. K. Silvon, and T. L. Dubina. Biological age and its estimation. I. Studies of some physiological parameters in albino rats and their validity as biological age tests. Exp. Gerontol. 16: 13–24, 1981.
 142. Dziewiatkowski, D. D., J. La Valley, and A. G. Beaudoin. Age‐related changes in the composition of proteoglycans in sheep cartilages. Connect. Tissue Res. 19: 103–120, 1989.
 143. Eaton, J. W. Is the lens canned? Free Radic. Biol. Med. 11: 207–213, 1991.
 144. Eghbali, M., M. Eghbali, T. F. Robinson, S. Seifter, and O. O. Blumenfeld. Collagen accumulation in heart ventricles as a function of growth and aging. Cardiovasc. Res. 23: 723–729, 1989.
 145. Ehrhart, L. A., and C. M. Ferrario. Collagen metabolism and reversal of aortic hypertrophy in spontaneously hypertensive rats treated with methyldopa. Hypertension 3: 479–484, 1981.
 146. Elliott, R. J., and D. L. Gardner. Changes with age in the glycosaminoglycans of human articular cartilage. Ann. Rheum. Dis. 38: 371–377, 1979.
 147. Epstein, D. L., and J. H. Kinoshita. The effect of diamide on lens glutathione and lens membrane function. Invest. Ophthalmol. 9: 629–638, 1970.
 148. Esposito, C., H. Gerlach, J. Brett, D. Stern, and H. Vlassara. Endothelial receptor‐mediated binding of glucose‐modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J. Exp. Med. 170: 1387–1407, 1989.
 149. Everitt, A. V., and L. Delbridge. Two phases of collagen ageing in the tail tendon of hypophysectomized rats. Exp. Gerontol. 7: 45–51, 1972.
 150. Everitt, A. V., B. D. Porter, and M. Steele. Dietary, caging and temperature factors in the ageing of collagen fibres in rat tail tendon. Gerontology 27: 37–41, 1981.
 151. Everitt, A. V., N. J. Seedsman, and F. Jones. The effects of hypophysectomy and continuous food restriction, begun at ages 70–400 days, on collagen aging, proteinuria, incidence of pathology and longevity in the male rat. Mech. Ageing Dev. 12: 161–172, 1980.
 152. Everitt, A. V., J. R. Wyndham, and D. L. Barnard. The anti‐aging action of hypophysectomy in hypothalamic obese rats: effects on collagen aging, age‐associated proteinuria development and renal histopathology. Mech. Ageing Dev. 22: 233–251, 1983.
 153. Eyre, D. R., and H. Oguchi. The hydroxypyridinium crosslinks of skeletal collagens: their measurement, properties and a proposed pathway of formation. Biochem. Biophys. Res. Commun. 92: 403–410, 1980.
 154. Eyre, D. R., I. R. Dickson, and K. Van Ness. Collagen cross‐linking in human bone and articular cartilage: age‐related changes in the content of mature hydroxypyridinium residues. Biochem. J. 252: 495–500, 1988.
 155. Eyre, D. R., T. J. Koob, and K. P. Van Ness. Quantitation of hydroxypyridinium crosslinks in collagen by high‐performance liquid chromatography. Anal. Biochem. 137: 380–388, 1984.
 156. Eyre, D. R., M. A. Paz, and P. M. Gallop. Cross‐linking in collagen and elastin. Annu. Rev. Biochem. 53: 717–748, 1984.
 157. Farmar, J. G., P. C. Ulrich, and A. Cerami. Novel pyrroles from sulfite‐inhibited Maillard reactions: insight into the mechanism of inhibition. J. Org. Chem. 53: 2346–2349, 1988.
 158. Fazio, M. J., D. R. Olsen, H. Kuivaniemi, M.‐L. Chu, J. M. Davidson, J. Rosenbloom, and J. Uitto. Isolation and characterization of human elastin cDNAs, and age‐associated variation in elastin gene expression in cultured skin fibroblasts. Lab. Invest. 58: 270–277, 1988.
 159. Fecondo, J. V., and R. C. Augusteyn. Superoxide dismutase, catalase and glutathione peroxidase in human cataractous lens. Exp. Eye Res. 36: 15–23, 1983.
 160. Fedarko, N. S., U. K. Vetter, S. Weinstein, and P. G. Robey. Age‐related changes in hyaluronan, proteoglycan, collagen and osteonectin by human bone cells. J. Cell. Physiol. 151: 215–227, 1992.
 161. Feldman, S. A., and S. Glagov. Transmedial collagen and elastin gradients in human aortas: reversal with age. Atherosclerosis 13: 385–394, 1971.
 162. Fisher, R. F. The changes with age in the biophysical properties of the capsule of the human crystalline lens in relation to cataract. Interdiscipl. Top. Gerontol. 13: 131–142, 1978.
 163. Flandin, F., C. Buffevant, and D. Herbage. A differential scanning calorimetry analysis of the age‐related changes in the thermal stability of rat skin collagen. Biochim. Biophys. Acta 791: 205–211, 1984.
 164. Flandin, F., C. Buffevant, and D. Herbage. Age‐related changes in the biochemical and physiocochemical properties of rat skin. Collagen synthesis and maturation and mechanical parameters (uniaxial tension). Cell. Mol. Biol. 32: 565–571, 1986.
 165. Flannery, C. R., M. W. Lark, and J. D. Sandy. Identification of a stromelysin cleavage site within the interglobular domain of human aggrecan. J. Biol. Chem. 267: 1008–1014, 1992.
 166. Flannery, C., V. Stanescu, M. Morgelin, R. Boynton, J. Gordy, and J. Sandy. Variability in the G3 domain and content of bovine aggrecan from cartilage extracts and chondrocyte cultures. Arch. Biochem. Biophys. 297: 52–60, 1992.
 167. Flannery, C. R., P. J. Urbanek, and J. D. Sandy. The effect of maturation and aging on the structure and content of link proteins in rabbit articular cartilage. J. Orthop. Res. 8: 78–85, 1990.
 168. Fleishman, K. R., S. C. Margolis, J. Fu, and B. J. Wagner. Age changes in bovine lens endopeptidase activity. Mech. Ageing Dev. 31: 37–47, 1985.
 169. Fleischmajer, R., J. S. Perlish, and R. I. Bashey. Human dermal glycosaminoglycans and aging. Biochim. Biophys. Acta 279: 265–275, 1972.
 170. Fornieri, C., D. Quaglino, Jr., and G. Mori. Role of the extracellular matrix in age‐related modifications of the rat aorta: ultrastructural, morphometric, and enzymatic evaluations. Arterioscler. Thromb. 12: 1008–1016, 1992.
 171. Foster, J. A., and S. W. Curtiss. The regulation of lung elastin synthesis. Am. J. Physiol. 259: L13–L23, 1990.
 172. Foster, J. A., C. B. Rich, M. Miller, M. R. Benedict, R. A. Richman, and J. R. Florini. Effect of age and IGF‐1 administration on elastin gene expression in rat aorta. J. Gerontol. 45: B113–B118, 1990.
 173. Fourtanier, A., and C. Berrebi. Miniature pig as an animal model to study photoaging. Photochem. Photobiol. 50: 771–784, 1989.
 174. Francis, G., R. John, and J. Thomas. Biosynthetic pathway of desmosines in elastin. Biochem. J. 136: 45–55, 1973.
 175. Frank, C., D. McDonald, R. Lieber, and P. Sabiston. Biochemical heterogeneity within the maturing rabbit medial collateral ligament. Clin. Orthop. 236: 279–285, 1988.
 176. Front, P., F. Aprile, D. R. Mitrovic, and D. A. Swann. Age‐related changes in synthesis of matrix macromolecules by bovine articular cartilage. Connect. Tissue Res. 19: 121–133, 1989.
 177. Fu, M.‐X., K. J. Knecht, S. R. Thorpe, and J. W. Baynes. Role of oxygen in crosslinking and chemical modification of collagen by glucose. Diabetes 41 (suppl. 2): 42–48, 1992.
 178. Fucci, L., C. N. Oliver, M. J. Coon, and E. R. Stadtman. Inactivation of key metabolic enzymes by mixed‐function oxidation reactions: possible implication in protein turnover and ageing. Proc. Natl. Acad. Sci. USA 80: 1521–1525, 1983.
 179. Fujii, N., S. Muraoka, K. Satho, H. Hori, and K. Hanada. Racemization of aspartic acids at specific sites in αA‐crystallins from aged human lens. Biomed. Res. 12: 315–321, 1991.
 180. Fujimori, E. Crosslinking and fluorescence changes of collagen by glycation and oxidation. Biochim. Biophys. Acta 998: 105–110, 1989.
 181. Fujiimoto, D. Aging and crosslinking in human aorta. Biochem. Biophys. Res. Commun. 109: 1264–1269, 1982.
 182. Fujimoto, D. Aging of human connective tissue: increase in the content of a crosslinking amino acid, histidinoalanine. Biochem. Int. 5: 743–746, 1982.
 183. Fujimoto, D., and T. Moriguchi. Pyridinoline, a non‐reducible crosslink of collagen. J. Biochem. 83: 863–867, 1978.
 184. Fujimoto, D., M. Hirama, and T. Iwashita. Histidinoalanine, a new crosslinking amino acid, in calcified tissue collagen. Biochem. Biophys. Res. Commun. 104: 1102–1106, 1982.
 185. Fujimoto, D., T. Moriguchi, T. Ishida, and H. Hayashi. The structure of pyridinoline, a collagen crosslink. Biochem. Biophys. Res. Commun. 84: 52–57, 1978.
 186. Fujimoto, D., M. Suzuki, A. Uchiyama, S. Miyamoto, and T. Inoue. Analysis of pyridinoline, a crosslinking compound of collagen fibers, in human urine. J. Biochem. 94: 1133–1136, 1983.
 187. Furth, J. J. The steady‐state levels of type I collagen mRNA are reduced in senescent fibroblasts. J. Gerontol. 46: B122–B124, 1991.
 188. Garcia‐Castineiras, S., J. Dillon, and A. Spector. Non‐tryptophan fluorescence associated with human lens protein; apparent complexity and isolation of bityrosine and anthranilic acid. Exp. Eye Res. 26: 461–476, 1978.
 189. Garland, D. Role of site‐specific, metal catalyzed oxidation in lens aging and cataract: a hypothesis. Exp. Eye Res. 50: 677–682, 1990.
 190. Garland, D., P. Russell, and J. S. Zigler, Jr., The oxidative modification of lens proteins. In: Oxygen Radicals in Biology and Medicine, edited by Simic. Fig et al. New York: Plenum Press, 1988, vol. 49. p. 347–352.
 191. Garland, D., J. S. Zigler, Jr., and J. Kinoshita. Structural changes in bovine lens crystallins induced by ascorbate, metal and oxygen. Arch. Biochem. Biophys. 251: 771–776, 1986.
 192. Garlick, R. L., H. F. Bunn, and R. G. Spiro. Nonenzymatic glycation of basement membranes from human glomeruli and bovine sources. Diabetes 37: 1144–1150, 1988.
 193. Garlick, R. L., J. S. Mazer, and H. F. Bunn. Characterization of glycosylated hemoglobins: relevance to monitoring of diabetic control and analysis of other proteins. J. Clin. Invest. 71: 1062–1072, 1982.
 194. Garner, W. H., and A. Spector. Racemization in human lens. Evidence of rapid insolubilization of specific polypeptides in cataract formation. Proc. Natl. Acad. Sci. USA 75: 3618–3620, 1978.
 195. Garner, W. H., and A. Spector. A preliminary study of dynamic aspects of age‐dependent changes in the abundance of human lens polypeptides. Doc. Ophthalmol. (The Hague) 18: 91–99, 1979.
 196. Garner, W. H., and A. Spector. Selective oxidation of cysteine and methionine in normal and senile cataractous lenses. Proc. Natl. Acad. Sci. USA 77: 1274–1277, 1980.
 197. Garner, W. H., A. Bahador, and G. Sachs. Nonenzymatic glycation of Na,K‐ATPase: effects on ATP hydrolysis and K+ occlusion. J. Biol. Chem. 265: 15058–15063, 1990.
 198. Garner, W. H., M. H. Garner, and A. Spector. Comparison of the 10,000 and 43,000 dalton polypeptide populations isolated from the water soluble and insoluble fractions of human cataractous lenses. Exp. Eye Res. 29: 257–276, 1979.
 199. Garner, W. H., M. H. Garner, and A. Spector. Gamma‐crystallin, a major cytoplasmic polypeptide disulfide linked to membrane proteins in human cataract. Biochem. Biophys. Commun. 98: 439–447, 1981.
 200. Garner, W. H., M. H. Garner, and A. Spector. H2 O2‐induced uncoupling of bovine lens Na+, K+‐ATPase. Proc. Natl. Acad. Sci. USA 80: 2044–2048, 1983.
 201. Garner, W. H., G. M. Wang, and A. Spector. Stimulation of glucosylated lens epithelial Na, K‐ATPase by an aldose reductase inhibitor. Exp. Eye Res. 44: 339–345, 1987.
 202. Gerber, G., G. Gerber, and K. I. Altman. Studies on the metabolism of tissue proteins. I. Turnover of collagen labeled with proline‐U‐C14 in young rats. J. Biol. Chem. 235: 2653–2656, 1960.
 203. Ghosh, P., T. K. F. Taylor, and K. G. Braund. The variation of the glycosaminoglycans of the canine intervertebral disc with ageing. I. chondrodystrophoid breed. Gerontology 23: 87–98, 1977.
 204. Giblin, F. J., B. Chakrapani, and V. N. Reddy. The effects of x‐irradiation on lens reducing systems. Invest. Ophthalmol. Vis. Sci. 18: 468–475, 1979.
 205. Giblin, F. J., J. R. Reddan, L. Schrimpsher, D. C. Dziedzic, and V. N. Reddy. The reactive roles of glutathione redox cycle and catalase in the detoxification of H2 O2 by cultured rabbit epithelial cells. Exp. Eye Res. 50: 795–804, 1990.
 206. Gibson, M. A., J. S. Kumaratilake, and E. G. Cleary. The protein components of the 12‐nanometer microfibrils of elastic and nonelastic tissues. J. Biol. Chem. 264: 4590–4598, 1989.
 207. Gilchrest, B. A. Premature aging syndromes affecting the skin. Birth Defects 17: 227–241, 1981.
 208. Gillery, P., J. C. Monboisse, F. X. Maquart, and J. P. Borel. Glycation of proteins as a source of superoxide. Diabetes Metab. 14: 25–30, 1988.
 209. Godeau, G., and W. Hornebeck. Morphometric analysis of the degradation of human skin elastic fibres by human leukocyte elastase (EC 3‐4‐21‐37) and human skin fibroblast elastase (EC 3‐4‐24). Pathol. Biol. (Paris) 36: 1133–1138, 1988.
 210. Goldstein, S., Human genetic disorders that feature premature onset and accelerated progression of biological aging. In: The Genetics of Aging, edited by E. L. Schneider. New York: Plenum Press, 1978, p. 171–224.
 211. Gomez, E. C., and B. Berman. The aging skin. Clin. Geriatr. Med. 1: 285–305, 1985.
 212. Goosey, J. D., J. S. Zigler, Jr., I. B. C. Matheson, and J. H. Kinoshita. Effects of singlet oxygen on human lens crystallins in vitro. Invest. Ophthalmol. Vis. Sci. 20: 679–683, 1981.
 213. Gottrup, F. Healing of incisional wounds in the stomach and duodenum. Dan. Med. Bull. 31: 32–48, 1984.
 214. Gower, W. E., and V. Pedrini. Age‐related variations in protein polysaccharides from human nucleus pulposus, annulus fibrosus, and costal cartilage. J. Bone Joint Surg. 51A: 1154–1162, 1969.
 215. Grandhee, S. K., and V. M. Monnier. Mechanism of formation of the Maillard protein crosslink pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. J. Biol. Chem. 266: 11649–11653, 1991.
 216. Grasedyck, K., M. Jahnke, O. Friedrich, D. Schulz, and I. Lindner. Aging of liver: morphological and biochemical changes. Mech. Ageing Dev. 14: 435–442, 1980.
 217. Greenwald, S. E., C. L. Berry, and R. E. Ramsey. The static elastic properties and chemical composition of the rat aorta in spontaneously occurring and experimentally induced hypertension: the effect of an anti‐hypertensive drug. Br. J. Exp. Path. 66: 633–642, 1985.
 218. Groenen, P. J. T. A., P. R. L. A. van den Ijseel, C. E. M. Voorter, H. Bloemendal, and W. W. de Jong. Site‐specific racemization in aging αA‐crystallin. FEBS Lett. 269: 109–112, 1990.
 219. Grundboeck‐Jusco, J., A. Binette, A. Kimura, L. Talarico, R. Kaelin, and K. Schmid. The glycosaminoglycan composition of the lung with acute and chronic pathology and in senescence. Clin. Chim. Acta 208: 77–84, 1992.
 220. Grushko, G., R. Schneiderman, and A. Maroudas. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and the degeneration in human hip cartilage. Connect. Tissue Res. 19: 149–176, 1989.
 221. Guantieri, V., A. M. Tamburro, and D. D. Gordini. Interactions of human and bovine elastins with lipids: their proteolysis by elastase. Connect. Tissue Res. 12: 79–83, 1983.
 222. Gunja‐Smith, Z., J. Lin, and J. F. Woessner. Changes in desmosine and pyridinoline crosslinks during rapid synthesis and degradation of elastin and collagen in the rat uterus. Matrix 9: 21–27, 1989.
 223. Gutierrez, P. S., I. C. de Almeida, H. B. Nader, M. de Lourdes Higuchi, N. Stolf, and C. P. Dietrich. Decrease in sulphated glycosaminoglycans in aortic dissection—possible role in the pathogenesis. Cardiovasc. Res. 25: 742–748, 1991.
 224. Guyton, J. R., K. L. Lindsay, and D. T. Dao. Comparison of aortic intima and inner media in young adult versus aging rats. Stereology in a polarized system. Am. J. Pathol. 111: 234–246, 1983.
 225. Hall, D. A., The metabolism of connecttissue. In: The Ageing of Connective Tissue, edited by D. A. Hall. New York: Academic Press, 1976, p. 145–171.
 226. Ham, W. T., Jr., H. A. Mueller, J. J. Ruffalo, Jr., D. Guerry, III, and R. K. Guerry. Action spectrum for retinal injury from near‐ultraviolet radiation in the aphakic monkey. Am. J. Ophthalmol. 93: 299–306, 1982.
 227. Hamlin, C. R., R. R. Kohn, and J. L. Luschin. Apparent accelerated aging of collagen in diabetes mellitus. Diabetes 24: 902–904, 1975.
 228. Hamlin, C. R., J. H. Luschin, and R. R. Kohn. Partial characterization of the age‐related stabilizing factor of post‐mature human collagen‐I. By use of bacterial collagenase. Exp. Gerontol. 13: 403–414, 1978.
 229. Hamlin, C. R., J. H. Luschin, and R. R. Kohn. Aging of collagen: comparative rates in four mammalian species. Exp. Gerontol. 15: 393–398, 1980.
 230. Harding, J. J. Free and protein‐bound glutathione in normal and cataractous human lenses. Biochem. J. 117: 957–960, 1970.
 231. Harding, J. J. Conformational changes in human lens proteins in cataract. Biochem. J. 129: 97–103, 1972.
 232. Harding, J. J., and K. J. Dilley. Structural proteins of the mammalian lens: a review with emphasis on changes in development, aging and cataract. Exp. Eye Res. 22: 1–73, 1976.
 233. Harding, J. J., and R. van Heyningen. Epidemiology and risk factors for cataract eye. Eye 1: 537–541, 1987.
 234. Hardingham, T., and M. Bayliss. Proteoglycans of articular cartilage: changes in aging and in joint disease. Semin. Arthritis Rheum. 20 (suppl. 1): 12–33, 1990.
 235. Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11: 289–300, 1956.
 236. Harris, E. D., and S. M. Krane. Collagenases. N. Engl. J. Med. 291: (Parts 1–3), 557–564, 605–610, 652–661, 1974.
 237. Harris, P., D. Heath, and A. Apostolopoulos. Extensibility of human pulmonary trunk. Br. Heart J. 27: 651–659, 1965.
 238. Harrison, D. E., and J. R. Archer. Physiological assays for biological age in mice: relationship of collagen, renal function, and longevity. Exp. Aging Res. 9: 245–251, 1983.
 239. Harrison, D. E., and J. R. Archer. Genetic differences in effects of food restriction on aging in mice. J. Nutr. 117: 376–382, 1987.
 240. Harrison, D. E., J. R. Archer, and C. M. Astle. Effects of food restriction on aging: separation of food intake and adiposity. Proc. Natl. Acad. Sci. USA 81: 1835–1838, 1984.
 241. Harrison, D. E., J. R. Archer, G. A. Sacher, and F. M. Boyce, III.. Tail collagen aging in mice of thirteen different genotypes and two species: relationship to biological age. Exp. Gerontol. 13: 63–73, 1978.
 242. Hashimoto, S., T. Yokokura, and M. Mutai. Effect of age and dietary composition on aortic collagen to elastin ratio and on lipid metabolism in F‐344 rat. Exp. Gerontol. 16: 35–39, 1981.
 243. Hata, R. Age‐dependent changes in collagen metabolism and response to hypertonic culture conditions of rat aortic smooth muscle cells in skin fibroblasts. Cell Biol. Int. Rep. 14: 25–33, 1990.
 244. Hayase, F., R. H. Nagaraj, S. Miyata, F. G. Njoroge, and V. M. Monnier. Aging of proteins: immunological detection of a glucose‐derived pyrrole formed during Maillard reaction in vivo. J. Biol. Chem. 263: 3758–3764, 1989.
 245. Hayashi, K., S. Nagasawa, Y. Naruo, A. Okumura, K. Moritake, and H. Handa. Mechanical properties of human cerebral arteries. Biorheology 17: 211–218, 1980.
 246. Heinegard, D., and A. Oldberg. Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 3: 2042–2051, 1989.
 247. Helin, P., C. Garbarsch, G. Helin, and I. Lorenzen. Vascular injury compared to ageing of normal rabbit aorta. Biochemical and histochemical studies on time‐dependent alterations of vascular connective tissue. Blood Vessels 22: 94–105, 1985.
 248. Heller, D. A., and G. E. Mcclearn. A longitudinal genetic study of tail tendon fibre break time. Age Ageing 21: 129–134, 1992.
 249. Herbrink, P., and H. Bloemendal. Studies on β‐crystallin. I. Isolation and partial characterization of the principal polypeptide chain. Biochim. Biophys. Acta 336: 370–382, 1974.
 250. Hicks, M., L. Delbridge, D. K. Yue, and T. S. Reeve. Increase in crosslinking of nonenzymatically glycosylated collagen induced by products of lipid peroxidation. Arch. Biochem. Biophys. 268: 249–254, 1989.
 251. Higgins, K. A., J. T. Stout, D. A. Heller, and R. F. Parker. Individual variability in tail tendon fiber break time in three age cohorts of different strains of mice. Exp. Gerontol. 26: 467–477, 1991.
 252. Hockwin, O. Enzyme activities in relationship to age and phosphorylated intermediates in energy metabolism. Invest. Ophthalmol. 4: 496–501, 1965.
 253. Hofecker, G., M. Skalicky, A. Kment, and H. Niedermüller. Models of biological age of the rat. I. A factor model of age parameters. Mech. Ageing Dev. 14: 345–359, 1980.
 254. Hogan, M. J., J. A. Alvarado, and J. E. Weddell, (Eds). In: Histology of the Human Eye, Philadelphia: W. B. Saunders, 1971, p. 435.
 255. Hollander, D., A. Tarnawski, J. Stachura, and H. Gergely. Morphologic changes in gastric mucosa of aging rats. Dig. Dis. Sci. 34: 1692–1700, 1989.
 256. Hollmann, J., A. Schmidt, D.‐B. von Bassewitz, and E. Buddecke. Relationship of sulfated glycosaminoglycans and cholesterol content in normal and arteriosclerotic human aorta. Arteriosclerosis 9: 154–158, 1989.
 257. Holmes, M. W. A., M. T. Bayliss, and H. Muir. Hyaluronic acid in human cartilage: age‐related changes in content and size. Biochem. J. 250: 435–441, 1988.
 258. Honda, T., K. Katagiri, E. Kuroda, E. Matsunaga, and H. Shinkai. Age‐related changes of the dermatan sulfate containing small proteoglycans in bovine tendon. Collagen Rel. Res. 7: 171–184, 1987.
 259. Horiuchi, S., N. Araki, and Y. Morino. Immunochemical approach to characterize advanced glycation end products of the Maillard reaction. J. Biol. Chem. 266: 7329–7332, 1991.
 260. Horiuchi, S., M. Shiga, N. Araki, K. Takata, M. Saitoh, and Y. Morino. Evidence against in vivo presence of 2‐(2‐furoyl)‐4(5)‐(2‐furanyl)‐1H‐imidazole, a major fluorescent advanced end product generated by nonenzymatic glycosylation. J. Biol. Chem. 263: 18821–18826, 1988.
 261. Hormel, S. E., and D. R. Eyre. Collagen in the ageing human intervertebral disc: an increase in covalently bound fluorophores and chromophores. Biochim. Biophys. Acta 1078: 243–250, 1991.
 262. Horn, P. L., J. J. Laver, and J. T. Wood. Changes of aging parameters among rats on diets differing in fat quantity and quality. J. Gerontol. 36: 285–293, 1981.
 263. Hornebeck, W., J. J. Adnet, and L. Robert. Age‐dependent variation of elastin and elastase in aorta and human breast cancers. Exp. Gerontol. 13: 293–298, 1978.
 264. Horowitz, J., and M. M. Wong. Peptide mapping by limited proteolysis in sodium dodecyl sulfate of the main intrinsive polypeptides isolated from human and bovine lens plasma membranes. Biochim. Biophys. Acta 622: 134–143, 1980.
 265. Horowitz, J., J. S. Hansen, C. C. Cheng, L. L. Ding, B. R. Straatsma, D. O. Lightfoot, and L. J. Takemoto. Presence of low molecular weight polypeptides in human brunescent cataracts. Biochem. Biophys. Res. Commun. 113: 65–71, 1983.
 266. Hricik, D. E., J. A. Schulak, D. R. Sell, J. F. Fogarty, and V. M. Monnier. Effects of kidney or kidney‐pancreas transplantation on plasma pentosidine. Kidney Int. 43: 398–403, 1993.
 267. Huang, K.‐C., K. Sukegawa, and T. Orii. Glycosaminoglycan excretion in random samples of urine. Clin. Chim. Acta 151: 141–146, 1985.
 268. Huber, B., F. Ledl, T. Severin, A. Stangl, and G. Pfleiderer. Formation of 2‐(2‐furoyl)‐4(5)‐(2‐furyl)‐1H‐imidazole in the Maillard reaction. Carbohydr. Res. 182: 301–306, 1988.
 269. Huby, R., and J. J. Harding. Nonenzymatic glycosylation (glycation) of lens proteins by galactose and protection by aspirin and reduced glutathione. Exp. Eye Res. 47: 53–59, 1988.
 270. Hunt, J. V., R. T. Dean, and S. P. Wolff. Hydroxyl radical production and autoxidative glycosylation: glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem. J. 256: 205–212, 1988.
 271. Imayama, S., and I. M. Braverman. A hypothetical explanation for the aging of skin: chronologic alteration of the three‐dimensional arrangement of collagen and elastic fibers in connective tissue. Am. J. Pathol. 134: 1019–1025, 1989.
 272. Indik, Z., H. Yeh, N. Ornstein‐Goldstein, U. Kucich, W. Abrams, J. C. Rosenbloom, and J. Rosenbloom. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. Am. J. Med. Genet. 34: 81–90, 1989.
 273. Indik, Z., H. Yeh, N. Ornstein‐Goldstein, P. Sheppard, N. Anderson, J. C. Rosenbloom, L. Peltonen, and J. Rosenbloom. Alternate splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Proc. Natl. Acad. Sci. USA 84: 5680–5684, 1987.
 274. Indrekvam, K., I. Vikoyr, R. T. Lie, L. B. Engesaeter, and N. Langeland. Age‐related differences in chemical composition of rat femur as determinants for strain. Acta Orthop. Scand. 62: 455–458, 1991.
 275. Ingram, D. K., J. R. Archer, and D. E. Harrison. Physiological and behavioral correlates of lifespan in aged C57BL/6J mice. Exp. Gerontol. 17: 295–303, 1982.
 276. Ippolito, E., P. G. Natali, F. Postacchini, L. Accinni, and C. De Martino. Morphological, immunochemical and biochemical study of rabbit Achilles tendon at various ages. J. Bone Joint Surg. 62: 583–598, 1980.
 277. Isemura, M., K. Takahashi, and T. Ikenaka. Comparative study of carbohydrate‐protein complexes. II. Determination of hydroxylysine and its glycosides in human skin and scar collagens by an improved method. J. Biochem. 80: 653–658, 1976.
 278. Ishii, T., H. Tsuji, A. Sano, Y. Katoh, H. Matsui, and N. Terahata. Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc. J. Orthop. Res. 9: 78–90, 1991.
 279. Ito, A., H. Yamagiwa, and R. Sasaki. Effects of aging on hydroxyproline in human heart muscle. J. Am. Geriatr. Soc. 28: 398–404, 1980.
 280. Jackson, S. H., and J. A. Heininger. A reassessment of the collagen reutilization theory by an isotope ratio method. Clin. Chim. Acta 46: 153–160, 1973.
 281. Jackson, S. H., and J. A. Heininger. A study of collagen reutilization using an 18O2 labeling technique. Clin. Chim. Acta 51: 163–171, 1974.
 282. Jackson, S. H., and J. A. Heininger. Proline recycling during collagen metabolism as determined by concurrent 18O2‐and 3H‐labeling. Biochim. Biophys. Acta 381: 359–367, 1975.
 283. Jahngen, J. H., A. L. Haas, A. Ciechanover, J. Blondin, D. Eisenhauer, and A. Taylor. The eye lens has an active ubiquitin‐protein conjugation system. J. Biol. Chem. 261: 13760–13767, 1986.
 284. Jedziniak, J., and J. Rokita. Aldehyde metabolism in the human lens. Exp. Eye Res. 37: 119–127, 1983.
 285. Jedziniak, J. A., L. M. Arredondo, and L. Meys. Human lens enzyme alterations with age and cataract. Glyceraldehyde‐6‐P dehydrogenase and triose phosphate isomerase. Curr. Eye Res. 119–126, 1986.
 286. Jedziniak, J. A., L. T. Chylack, Jr., H.‐M. Cheng, M. K. Gillis, A. A. Kalustian, and W. H. Tung. The sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase. Invest. Ophthalmol. Vis. Sci. 20: 314–326, 1981.
 287. Jedziniak, J. A., J. H. Kinoshita, E. M. Yates, L. O. Hocher, and G. B. Benedek. On the presence and mechanism of formation of heavy molecular weight aggregates in human normal and cataractous lenses. Exp. Eye Res. 15: 185–192, 1973.
 288. Jernigan, H. M., Jr., H. N. Fukui, J. D. Gossey, and J. H. Kinoshita. Photodynamic effects of rose bengal or riboflavin on carrier‐mediated transport systems in rat lens. Exp. Eye Res. 32: 461–466, 1981.
 289. Jha, M. Age‐related changes in pyridinoline content of rabbit collagen. Exp. Gerontol. 17: 7–9, 1982.
 290. John, R., and J. Thomas. Chemical compositions of elastins isolated from aortas and pulmonary tissues of humans of different ages. Biochem. J. 127: 261–269, 1972.
 291. Kadar, A. Scanning electron microscopy of purified elastin with and without enzymatic digestion. Adv. Exp. Med. Biol. 79: 71–96, 1977.
 292. Kamei, A., and M. Kato. Contribution of glycation to human lens coloration. Chem. Pharm. Bull. 39: 1272–1276, 1991.
 293. Kanayama, T., Y. Miyanaga, K. Horiuchi, and D. Fujimoto. Detection of the crosslinking amino acid, histidinoalanine, in human brown cataractous protein. Exp. Eye Res. 44: 165–169, 1987.
 294. Kanungo, M. S., Changes in collagen. In: Biochemistry of Ageing, edited by M. S. Kanungo. New York: Academic Press, 1980, p. 129–157.
 295. Kao, K.‐Y., D. M. Hilker, and T. H. McGavack. Connective tissue V. Comparison of synthesis and turnover of collagen and elastin in tissues of rat at several ages. Proc. Soc. Exp. Biol. Med. 106: 335–338, 1961.
 296. Karttunen, T., J. Risteli, H. Autio‐Harmainen, and L. Risteli. Effect of age and diabetes on type IV collagen and laminin in human kidney cortex. Kidney Int. 30: 586–591, 1986.
 297. Karwatowski, W. S., T. E. Jefferies, V. C. Duance, J. Albon, A. J. Bailey, and D. L. Easty. Collagen and ageing in Bruch's membrane. Biochem. Soc. Trans. 19: 349S, 1991.
 298. Kasuya, M., M. Itoi, S. Kobayashi, H. Sunaga, and K. T. Suzuki. Changes of glutathione and taurine concentrations in lenses of rat eye induced by galactose‐cataract formation or aging. Exp. Eye Res. 54: 49–53, 1992.
 299. Kato, H., N. van Chuyen, T. Shinoda, F. Sekiya, and F. Hayase. Metabolism of 3‐deoxyglucosone, an immediate compound in the Maillard reaction, administered orally or intravenously to rats. Biochim. Biophys. Acta 1035: 71–76, 1990.
 300. Kemp, P. D., and J. E. Scott. Ehrlich chromogens, probable cross‐links, in elastin and collagen. Biochem. J. 252: 387–393, 1988.
 301. Kerr, J. S., S. Y. Yu, and D. J. Riley. Strain specific respiratory air space enlargement in aged rats. Exp. Gerontol. 25: 563–574, 1990.
 302. Kettelhut, B. V., and D. D. Metcalfe. Quantitation and characterization of urinary glycosaminoglycans in healthy subjects and patients with mastocytosis. Clin. Chim. Acta 171: 29–36, 1988.
 303. klbrick, A. C., and K. D. Singh. Hydroxyproline excreted in the urine: its source from collagen of tissues after 14C‐proline in rats with and without administration of prednisone. J. Clin. Endocrinol. Metab. 38: 594–601, 1974.
 304. Kikugawa, K., and M. Beppu. Involvement of lipid oxidation products in the formation of fluorescent and crosslinked proteins. Chem. Phys. Lipids 44: 277–296, 1987.
 305. Kittlick, P.‐D. Glycosaminoglycans. Recent biochemical results in the fields of growth and inflammation. Exp. Pathol. 10 (suppl): 1–174, 1985.
 306. Kivirikko, K. I. Urinary excretion of hydroxyproline in health and disease. Int. Rev. Connect. Tissue Res. 5: 93–163, 1970.
 307. Knecht, K. J., J. A. Dunn, K. F. McFarland, D. R. McCance, T. J. Lyons, S. R. Thorpe, and J. W. Baynes. Effect of diabetes and aging on carboxymethyllysine levels in human urine. Diabetes 40: 190–196, 1991.
 308. Knecht, K. J., M. S. Feather, and J. W. Baynes. Detection of 3‐deoxyfructose and 3‐deoxyglucosone in human urine and plasma: evidence for intermediate stages of the Maillard reaction in vivo. Arch. Biochem. Biophys. 294: 130–137, 1992.
 309. Kobayashi, Y., and T. Suzuki. The aging lens: ultrastructural changes in cataract. In: Cataract and Abnormalities of the Lens, edited by J. G. Bellows. New York: Grune and Stratton, 1975, p. 313–343.
 310. Kodama, T., and L. Takemoto. Characterization of disulfide‐linked crystallins associated with human cataractous lens membranes. Invest. Ophthalmol. Vis. Sci. 29: 145–149, 1988.
 311. Kodama, T., V. N. Reddy, F. J. Giblin, J. H. Kinoshita, and C. Harding. Scanning electron microscopy of x‐ray induced cataract in mice on normal and galactose diet. Ophthalmol. Res. 15: 324–333, 1983.
 312. Kohn, R. R. Principles of Mammalian Aging. Englewood Cliffs, NJ: Prentice‐Hall, 1978.
 313. Kohn, R. R., Evidence against cellular aging theories. In: Testing the Theories of Aging, edited by R. C. Adelman and G. S. Roth. Boca Raton, FL: CRC Press, 1982, p. 221–232.
 314. Kohn, R. R. Effects of age and diabetes mellitus on cyanogen bromide digestion of human dura mater collagen. Connect. Tissue Res. 11: 169–173, 1983.
 315. Kohn, R. R., and V. M. Monnier. Normal aging and its parameters. In: Clinical Pharmacology in the Elderly, edited by C. G. Swift. New York: Marcel Dekker, 1987.
 316. Kohn, R. R., and E. Rollerson. Age changes in swelling properties of human myocardium. Proc. Soc. Exp. Biol. Med. 100: 253–256, 1959.
 317. Kohn, R. R., and S. L. Schnider. Glucosylation of human collagen. Diabetes 31 (suppl 3): 47–51, 1982.
 318. Kontermann, K., and K. Bayreuther. The cellular aging of rat fibroblasts in vitro is a differentiation process. Gerontology 25: 261–274, 1979.
 319. Kovanen, V. Effects of ageing and physical training on rat skeletal muscle. An experimental study on the properties of collagen, lamini, and fibre types in muscles serving different functions. Acta Physiol. Scand. 577 (suppl): 1–56, 1989.
 320. Kovanen, V., H. Suominen, and L. Peltonen. Effects of aging and life‐long physical training on collagen in slow and fast skeletal muscle in rats. Cell Tissue Res. 248: 247–255, 1987.
 321. Kovanen, V., H. Suominen, J. Risteli, and L. Risteli. Type IV collagen and laminin in slow and fast skeletal muscle in rats—effects of age and life‐time endurance training. Coll. Relat. Res. 8: 145–153, 1988.
 322. Krane, S. M., F. G. Kantrowitz, M. Byrne, S. R. Pinnell, and F. R. Singer. Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation. J. Clin. Invest. 59: 819–827, 1977.
 323. Krause, A. C. Chemistry of the lens. V. Relation of the anatomic distribution of the lenticular proteins to their chemical composition. Arch. Ophthalmol. 10: 788–792, 1933.
 324. Kristal, B. S., and B. P. Yu. An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions. J. Gerontol. 47: B107–B114, 1992.
 325. Krumpe, P. E., R. J. Knudson, G. Parsons, and K. Reiser. The aging respiratory system. Clin. Geriatr. Med. 1: 143–175, 1985.
 326. Kuller, L. H. Epidemiology of cardiovascular disease: current perspectives. Am. J. Epidemiol. 104: 425, 1976.
 327. Kurzel, R. B., M. L. Wolbarsht, and B. S. Yamanashi. Spectral studies on normal and cataractous intact human lenses. Exp. Eye Res. 17: 65–71, 1973.
 328. Kurzel, R. B., M. L. Wolbarsht, and B. S. Yamanashi. Ultraviolet radiation effects on the human eye. Photochem. Photobiol. Rev. 2: 133–167, 1977.
 329. Kuwabara, T. The maturation of the lens cell: a morphologic study. Exp. Eye Res. 20: 427–443, 1975.
 330. Kuypers, R., M. Tyler, L. B. Kurth, I. D. Jenkins, and D. J. Horgan. Identification of the loci of the collagen‐associated Ehrlich chromogen in type I collagen confirms its role as a trivalent crosslink. Biochem. J. 283: 129–136, 1992.
 331. Labella, F. S., Cross‐links in elastin and collagen. In: Biophysical Properties of the Skin, edited by H. R. Elden. New York: John Wiley and Sons, 1971, p. 243–301.
 332. Labella, F. S. Enzymatic vs. nonenzymatic factors in the deterioration of connective tissue. Adv. Exp. Med. Biol. 43: 377–402, 1974.
 333. Labella, F. S., S. Vivian, and D. P. Thornhill. Amino acid composition of human aortic elastin as influenced by age. J. Gerontol. 21: 550–555, 1966.
 334. Lagier, P. R., and B. Exer. Etude de la composition chimique de tissus humains de nature conjonctive en rapport avec l'age: derme et aponevrose de la paroi abodominale, tendon d'Achille. Gerontologia 4: 39–59, 1960.
 335. Laitinen, O. The metabolism of collagen and its hormonal control in the rat: III. Collagen as a precursor of urinary hydroxyproline. Acta Endocrinologia [Suppl.] (Copenha) 120: 1–86, 1967.
 336. Lapolla, A., C. Gerhardinger, B. Pelli, A. Sturaro, E. DEL Favero, P. Traldi, G. Crepaldi, and D. Fedele. Absence of brown product FFI in nondiabetic and diabetic rat collagen. Diabetes 39: 57–61, 1990.
 337. Larking, P. W., B. W. McDonald, M. L. Taylor, and A. D. Kirkland. Urine glycosaminoglycans in a reference population: effects of age, body surface area, and postmenopausal status. Biochem. Med. Metab. Biol. 37: 246–254, 1987.
 338. Last, J. A., L. G. Armstrong, and K. M. Reiser. Biosynthesis of collagen crosslinks. Int. J. Biochem. 22: 559–564, 1990.
 339. Laurent, G. J. Rates of collagen synthesis in lung, skin, and muscle obtained in vivo by a simplified method using [3H]proline. Biochem. J. 206: 535–544, 1982.
 340. Laurent, G. J. Dynamic state of collagen: pathways of collagen degradation in vivo and their possible role in regulation of collagen mass. Am. J. Physiol. 252: C1–C9, 1987.
 341. Laurent, G. J., and R. J. McAnulty. Protein metabolism during bleomycin‐induced pulmonary fibrosis in rabbits: in vivo evidence for collagen accumulation because of increased synthesis and decreased degradation of the newly synthesized collagen. Am. Rev. Respir. Dis. 128: 82–88, 1983.
 342. Laurent, G. J., and M. P. Sparrow. Changes in RNA, DNA and protein content and the rates of protein synthesis and degradation during hypertrophy of the anterior latissimus dorsi muscle of the adult fowl (Gallus domesticus). Growth 41: 249–262, 1977.
 343. Laurent, G. J., R. J. McAnulty, and J. Gibson. Changes in collagen synthesis and degradation during skeletal muscle growth. Am. J. Physiol. 249: C352–C355, 1985.
 344. Lavker, R. M., P. Zheng, and G. Dong. Morphology of aged skin. Clin. Geriatr. Med. 5: 53–67, 1989.
 345. Lefevre, M., and R. B. Rucker. Aorta elastin turnover in normal and hypercholesterolemic Japanese quail. Biochim. Biophys. Acta 630: 519–529, 1980.
 346. Le Lous, M., L. Cohen‐Solal, J. C. Allain, J. Bonaventure, and P. Maroteaux. Age‐related evolution of stable collagen reticulation in human skin. Connect. Tissue Res. 13: 145–155, 1985.
 347. Lerman, S. Composition and formation of the insoluble protein fraction in the ocular lens. Can. J. Ophthalmol. 5: 152–159, 1970.
 348. Lerman, S. Biophysical aspects of corneal and lenticular transparency. Curr. Eye Res. 3: 3–14, 1984.
 349. Lerman, S., and R. Borkman. Spectroscopic evaluation and classification of the normal, aging and cataractous lens. Ophthalmol. Res. 8: 335–353, 1976.
 350. Lerman, S., and R. Borkman. Ultraviolet radiation in the aging and cataractous lens. Acta Ophthalmol. 58: 139–149, 1977.
 351. Lerman, S., and R. F. Borkman. Photochemistry and lens aging. Interdiscipl. Top. Gerontol. 13: 154–182, 1978.
 352. Lerman, S., K. Gardner, J. Megaw, and R. Borkman. Prevention of direct photosynthesized ultraviolet radiation to the ocular lens. Ophthalmic Res. 13: 284–292, 1981.
 353. Lerman, S., F. K. Kuck, R. Borkman, and E. Saker. Acceleration of an aging parameter (fluorogen) in the ocular lens. Ann. Ophthalmol. 8: 558–562, 1976.
 354. Lerman, S., F. K. Kuck, R. Borkman, and E. Saker. Induction, acceleration and prevention (in vitro) of an aging parameter in the ocular lens. Ophthalmic Res. 13: 154–182, 1976.
 355. Leske, M. C., L. T. Chylack, Jr., and S. Y. Wu. The lens opacities case‐control study. Risk factors of cataract. Arch. Ophthalmol. 109: 244–251, 1991.
 356. Levine, R. L. Oxidative modification of glutamine synthetase. I. Inactivation is due to the loss of one histidine residue. J. Biol. Chem. 258: 11823–11827, 1983.
 357. Levine, R. L., C. N. Oliver, M. J. Coon, and E. R. Stadtman. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis. Proc. Natl. Acad. Sci. USA 78: 2120–2124, 1981.
 358. Liang, J. N., and B. Chakrabarti. Sugar‐induced change in near ultraviolet circular dichroism of α‐crystallin. Biochem. Biophys. Res. Commun. 102: 180–189, 1981.
 359. Liang, J. N., and L. T. Chylack, Jr.. Age‐related change in protein conformation of normal human α‐crystallin. Lens Res. 2: 189–206, 1984.
 360. Liang, J. N., and L. T. Chylack. Spectroscopic study on the effects of nonenzymatic glycation in human α‐crystallin. Invest. Ophthalmol. Vis. Sci. 28: 790–794, 1987.
 361. Liang, J. N., and M. T. Rossi. In vitro nonenzymatic glycation and formation of browning products in the bovine lens α‐crystallin. Exp. Eye Res. 50: 367–371, 1990.
 362. Liang, J. N., S. K. Bose, and B. Chakrabarti. Age‐related changes in protein conformation in bovine lens crystallins. Exp. Eye Res. 40: 461–469, 1983.
 363. Liang, J. N., L. L. Hershorin, and L. T. Chylack. Nonenzymatic glycosylation in human diabetic crystallins. Diabetologia 29: 225–228, 1986.
 364. Liang, Z.‐Q., F. Hayase, and H. Kato. Purification and characterization of NADPH‐dependent 2‐oxoaldehyde reductase from porcine liver: a self‐defense enzyme preventing the advanced stage of the Maillard reaction. Eur. J. Biochem. 197: 373–379, 1991.
 365. Light, N. D., and A. J. Bailey. The chemistry of the collagen cross‐links. Purification and characterization of cross‐linked polymeric peptide material from mature collagen containing unknown amino acids. Biochem. J. 185: 373–381, 1980.
 366. Light, N. D., and A. J. Bailey. Molecular structure and stabilization of the collagen fibre. In: Biology of Collagen, edited by A. Viidik and J. Vuust. New York: Academic Press, 1980, p. 15–38.
 367. Lippman, R. D. Rapid in vivo quantification and comparison of hydroperoxides and oxidized collagen in aging mice, rabbits and man. Exp. Gerontol. 20: 1–5, 1985.
 368. Lopez, M. G., and M. S. Feather. The production of threose as a degradation product from L‐ascorbic acid. J. Carbohydr. Chem. 11: 799–806, 1992.
 369. Lorand, L., L. K. H. Hsu, G. E. Siefring, Jr., and N. S. Rafferty. Lens transglutaminase and cataract formation. Proc. Natl. Acad. Sci. USA 78: 1356–1360, 1981.
 370. Lovell, C. R., K. A. Smolenski, V. C. Duance, N. D. Light, S. Young, and M. Dyson. Type I and III collagen content and fibre distribution in normal human skin during ageing. Br. J. Dermatol. 117: 419–428, 1987.
 371. Lowry, O., N. J. Rosebrough, A. L. Farr, and R. J. Randall. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193: 265–275, 1951.
 372. Lunec, J., D. R. Blake, S. J. McCleary, S. Brailsford, and P. A. Bacon. Self‐perpetuating mechanisms of immunoglobulin G aggregation in rheumatoid inflammation. J. Clin. Invest. 76: 2084–2090, 1985.
 373. Lyons, T. J., K. E. Bailie, D. G. Dyer, J. A. Dunn, and J. W. Baynes. Decrease in skin collagen glycation with improved glycemic control in patients with insulin‐dependent diabetes mellitus. J. Clin. Invest. 87: 1910–1915, 1991.
 374. Lyons, T. J., G. Silvestri, J. A. Dunn, D. G. Dyer, and J. W. Baynes. Role of glycation in modification of lens crystallins in diabetic senile cataracts. Diabetes 40: 1010–1015, 1991.
 375. MacDonald, E., W. K. Lee, S. Hepburn, J. Bell, P. J. W. Scott, and M. H. Dominiczak. Advanced glycosylation end products in the mesenteric artery. Clin. Chem. 38: 530–533, 1992.
 376. Madsen, K., S. Moskalewski, K. von der Mark, and U. Friberg. Synthesis of proteoglycans, collagen, and elastin by cultures of rabbit auricular chondrocytes—relation to age of the donor. Dev. Biol. 96: 63–73, 1983.
 377. Maisel, H., C. V. Harding, J. R. Alcala, J. Kuszak, and R. Bradley. The morphology of the lens. In: Molecular and Cellular Biology of the Eye Lens, edited by H. Bloemendal. New York: John Wiley and Sons, pp. 49–84, 1981.
 378. Makita, Z., S. Radoff, E. J. Rayfield, Z. Yang, E. Skolnik, V. Delaney, E. A. Friedman, A. Cerami, and H. Vlassara. Advanced glycosylation endproducts in patients with diabetic nephropathy. N. Engl. J. Med. 325: 836–842, 1991.
 379. Makita, Z., H. Vlassara, A. Cerami, and R. Bucala. Immunochemical detection of advanced of glycosylation end products in vivo. J. Biol. Chem. 267: 5133–5138, 1992.
 380. Malik, N. S., S. J. Moss, N. Ahmed, A. J. Furth, R. S. Wall, and K. M. Meek. Ageing of the human corneal stroma: structural and biochemical changes. Biochim. Biophys. Acta 1138: 222–228, 1992.
 381. Maroudas, A., M. T. Bayliss, and M. F. Venn. Further studies on the composition of human femoral head cartilage. Ann. Rheum. Dis. 39: 514–523, 1980.
 382. Martens, M. F. W. C., and T. Hendriks. Collagen synthesis in explants from rat intestine. Biochim. Biophys. Acta 993: 252–258, 1989.
 383. Martenson, J., A. Jain, E. Stole, W. Frayer, P. A. M. Auld, and A. Meister. Inhibition of glutathione synthesis in the newborn rat. A model for endogenously produced oxidative stress. Proc. Natl. Acad. Sci. USA 88: 9360–9364, 1991.
 384. Martin, M., R. E. Nabout, C. Lafuma, F. Crechet, and J. Remy. Fibronectin and collagen gene expression during in vitro ageing of pig skin fibroblasts. Exp. Cell Res. 191: 8–13, 1990.
 385. Masoro, E. J. Physiological system markers of aging. Exp. Gerontol. 23: 391–394, 1988.
 386. Masoro, E. J., M. S. Katz, and C. A. McMahan. Evidence for the glycation hypothesis of aging from the food‐restricted rodent model. J. Gerontol. 44: B20–B22, 1989.
 387. Masoro, E. J., R. J. M. McCarter, M. S. Katz, and C. A. McMahan. Dietary restriction alters characteristics of glucose fuel use. J. Gerontol. 47: B202–B208, 1992.
 388. Massie, H. R., V. R. Aiello, M. E. Shumway, and T. Armstrong. Calcium, iron, copper, boron, collagen and density changes in bone with aging in C57BL/6J male mice. Exp. Gerontol. 25: 469–481, 1990.
 389. Masters, P. M., J. L. Bada, and J. S. Zigler. Aspartic acid racemization in the human lens during aging and in cataract formation. Nature 268: 71–73, 1977.
 390. Maurel, E., H. Bouissou, M. T. Pieraggi, M. Julian, M. Moczar, and L. Robert. Age‐dependent biochemical changes in dermal connective tissue. Relationship to histological and ultrastructural observations. Connect. Tissue Res. 8: 33–39, 1980.
 391. Maurel, E., C. A. Shuttleworth, and H. Bouissou. Interstitial collagens and ageing in human aorta. Virchows Arch [A]. 410: 383–390, 1987.
 392. Mays, P. K., J. E. Bishop, and G. J. Laurent. Age‐related changes in the proportion of types I and III collagen. Mech. Ageing Dev. 45: 203–212, 1988.
 393. Mays, P. K., R. J. McAnulty, J. S. Campa, A. D. Cambrey, and G. J. Laurent. Similar age‐related alterations in collagen metabolism in rat tissues in vivo and fibroblasts in vitro. Bio‐chem. Soc. Trans. 18: 957, 1990.
 394. Mays, P. K., R. J. McAnulty, J. S. Campa, and G. J. Laurent. Age‐related changes in collagen synthesis and degradation in rat tissues. Importance of degradation of newly synthesized collagen in regulating collagen production. Biochem. J. 176: 307–313, 1991.
 395. Mays, P. K., R. J. McAnulty, and G. J. Laurent. Age‐related changes in lung collagen metabolism: a role for degradation in regulating lung collagen production. Am. Rev. Respir. Dis. 140: 410–416, 1989.
 396. Mays, P. K., R. McAnulty, and G. J. Laurent. Age‐related changes in total protein and collagen metabolism in rat liver. Hepatology 14: 1224–1229, 1991.
 397. Mbuyi‐Muamba, J. M., and J. Dequeker. Age and sex variations on bone matrix proteins in Wistar rats. Growth 47: 301–315, 1983.
 398. McAnulty, R. J., and G. J. Laurent. Collagen synthesis and degradation in vivo. Evidence for rapid rates of collagen turnover with extensive degradation of newly synthesized collagen in tissues of the adult rat. Coll. Relat. Res. 7: 93–104, 1987.
 399. McClearn, G. E. Strategies for biomarker research: experimental and methodological design. Exp. Gerontol. 23: 245–255, 1988.
 400. McDevitt, C. A., and R. J. Webber. The ultrastructure and biochemistry of meniscal cartilage. Clin. Orthop. 252: 8–18, 1990.
 401. McFall‐Ngai, M., J. Horowitz, L. L. Ding, and L. Lacey. Age‐dependent changes in the heat‐stable crystallin, βBp, of the human lens. Curr. Eye Res. 5: 387–394, 1986.
 402. McNamara, M., and R. C. Augusteyn. The effects of hydrogen peroxide on lens proteins: a possible model for nuclear cataract. Exp. Eye Res. 38: 45–56, 1984.
 403. McNicol, D., and P. J. Roughley. Extraction and characterization of proteoglycan from human meniscus. Biochem. J. 185: 705–713, 1980.
 404. McPherson, J. D., D. H. Shilton, and D. J. Walton. Role of fructose in glycation and crosslinking of proteins. Biochemistry 27: 1901–1907, 1988.
 405. Mechanic, G., P. M. Gallop, and M. L. Tanzer. The nature of crosslinking in collagens from mineralized tissues. Biochem. Biophys. Res. Commun. 45: 644–653, 1971.
 406. Mellerio, J. Yellowing of the human lens. Nuclear and cortical contributions. Vision Res. 27: 1581–1587, 1987.
 407. Miksik, I., and Z. Deyl. Change in the amount of ε‐hexosylly‐sine, UV absorbance, and fluorescence of collagen with age in different animal species. J. Gerontol. 46: B111–B116, 1991.
 408. Miksik, I., R. Struzinsky, and Z. Deyl. Change with age of UV absorbance and fluorescence of collagen and accumulation of ε‐hexosyllysine in collagen from Wistar rats living on different food restriction regimes. Mech. Ageing Dev. 57: 163–174, 1991.
 409. Millis, A. J. T., J. Sottile, M. Hoyle, D. M. Mann, and V. Diemer. Collagenase production by early and late passage of cultures of human fibroblasts. Exp. Gerontol. 24: 559–575, 1989.
 410. Miyahara, T., A. Murai, T. Tanaka, S. Shiozawa, and M. Kameyama. Age‐related differences in human skin collagen: solubility in solvent, susceptibility to pepsin digestion, and the spectrum of the solubilized polymeric collagen molecules. J. Gerontol. 37: 651–655, 1982.
 411. Miyata, S., and V. M. Monnier. Immunohistochemical detection of advanced glycosylation end products in diabetic tissues using monoclonal antibody to pyrraline. J. Clin. Invest. 89: 1102–1112, 1992.
 412. Moczar, M., J. Ouzilou, Y. Courtois, and L. Robert. Age dependence of the biosynthesis of intercellular matrix macro‐molecules of rabbit aorta in organ culture and cell culture. Gerontology 22: 461–472, 1976.
 413. Mohan, S., and E. Radha. Age‐related changes in rat muscle collagen. Gerontology 26: 61–67, 1980.
 414. Mohan, S., and E. Radha. Hydroxyproline excretion and collagen catabolism in rats of different age groups. Biochem. Med. 24: 1–5, 1980.
 415. Mohan, S., and E. Radha. Age‐related changes in muscle connective tissue: acid mucopolysaccharides and structural glycoprotein. Exp. Gerontol. 16: 385–392, 1981.
 416. Mollenhauer, J., and K. Bayreuther. Donor‐age‐related changes in morphology, growth potential, and collagen biosynthesis in rat fibroblasts subpopulations in vitro. Differentiation 32: 165–172, 1986.
 417. Molnar, J. A., N. M. Alpert, J. F. Burke, and V. R. Young. Synthesis and degradation rates of collagens in vivo in whole skin of rats, studies with 18O2 labeling. Biochem. J. 240: 431–435, 1986.
 418. Molnar, J. A., N. M. Alpert, J. F. Burke, and V. R. Young. Relative and absolute changes in soluble and insoluble collagen pool size in skin during normal growth and with dietary protein restriction in rats. Growth 51: 132–145, 1987.
 419. Molnar, J. A., N. M. Alpert, D. A. Wagner, S. Miyatani, J. F. Burke, and V. R. Young. Synthesis and degradation of collagens of skin of healthy and protein‐malnourished rats in vivo, studied by 18O2 labeling. Biochem. J. 250: 71–76, 1988.
 420. Monboisse, J. C., and J. P. Borel. Oxidative damage to collagen. In: Free Radicals and Aging, edited by I. Emerit and B. Chance. Boston: Birkhäuser Verlag, 1992, p. 323–327.
 421. Monnier, V. M. Nonenzymatic glycosylation, the Maillard reaction and the aging process. J. Gerontol. 45: B105–B111, 1990.
 422. Monnier, V. M., Toward a Maillard reaction theory of aging. In: The Maillard Reaction in Aging, Diabetes, and Nutrition, edited by J. W. Baynes and V. M. Monnier. New York: Alan R. Liss, 1989, p. 1–22.
 423. Monnier, V. M., and A. Cerami. Nonenzymatic browning in vivo: possible process for aging of long‐lived proteins. Science 211: 491–493, 1981.
 424. Monnier, V. M., and A. Cerami. Detection of nonenzymatic browning products in the human lens. Biochim. Biophys. Acta 760: 97–103, 1983.
 425. Monnier, V. M., R. R. Kohn, and A. Cerami. Accelerated age‐related browning of human collagen in diabetes mellitus. Proc. Natl. Acad. Sci. USA 81: 583–587, 1984.
 426. Monnier, V. M., D. R. Sell, R. H. Nagaraj, and S. Miyata. Mechanisms of protection against damage mediated by the Maillard reaction in aging. Gerontology 37: 152–165, 1991.
 427. Monnier, V. M., V. J. Stevens, and A. Cerami. Nonenzymatic glycosylation, sulfhydryl oxidation and aggregation of lens protein in experimental sugar cataracts. J. Exp. Med. 50: 1098–1107, 1970.
 428. Monnier, V. M., V. Vishwanath, K. E. Frank, C. A. Elmets, P. Dauchot, and R. R. Kohn. Relation between complications of type I diabetes mellitus and collagen‐linked fluorescence. N. Engl. J. Med. 314: 403–408, 1986.
 429. Montfort, I., and R. Pérez‐Tamayo. The muscle‐collagen ratio in normal and hypertrophic human hearts. Lab. Invest. 11: 463–470, 1962.
 430. Montfort, I., and R. Pérez‐Tamayo. The distribution of collagenase in normal rat tissues. J. Histochem. Cytochem. 23: 910–920, 1975.
 431. Mooradian, A. D. Biomarkers of aging: do we know what to look for? J. Gerontol. 45: B183–B186, 1990.
 432. Moriguchi, T., and D. Fujimoto. Age‐related changes in the content of the collagen crosslink, pyridinoline. J. Biochem. 84: 933–935, 1978.
 433. Mort, J. S., B. Caterson, A. R. Poole, and P. J. Roughley. The origin of human cartilage proteoglycan link‐protein heterogeneity and fragmentation during aging. Biochem. J. 232: 805–812, 1985.
 434. Mostapafour, M. K., and V. N. Reddy. Interactions of glutathione disulfide with lens crystallins. Curr. Eye Res. 2: 591–596, 1982–1983.
 435. Mullarkey, C. J., D. Edelstein, and M. Brownlee. Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem. Biophys. Res. Commun. 173: 932–939, 1990.
 436. Murata, K., and Y. Yokoyama. Acidic glycosaminoglycans in human atherosclerotic cerebral arterial tissues. Atherosclerosis 78: 69–79, 1989.
 437. Myers, B., M. Dubick, J. A. Last, and R. B. Rucker. Elastin synthesis during perinatal lung development in the rat. Biochim. Biophys. Acta 761: 17–22, 1983.
 438. Nagaraj, R. H., and V. M. Monnier. Isolation and characterization of a blue fluorophore from human eye lens crystallins: in vitro formation from Maillard reaction with ascorbate and ribose. Biochim. Biophys. Acta 1116: 34–42, 1992.
 439. Nagaraj, R. H., D. R. Sell, M. Prabhakaram, B. J. Ortwerth, and V. M. Monnier. High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis. Proc. Natl. Acad. Sci. USA 88: 10257–10261, 1991.
 440. Nakada, T., I. Sasagawa, H. Furuta, T. Katayama, and J. Shimazaki. Age‐related differences in norephinephrine and non‐collagenous protein in human vas deferens. J. Urol. 141: 998–1002, 1989.
 441. Nakayama, H., T. Mitsuhashi, S. Kuwajima, S. Aoki, Y. Kuroda, T. Itoh, and S. Nakagawa. Immunochemical detection of advanced glycation end products in lens crystallins from streptozocin‐induced diabetic rat. Diabetes 42: 345–350, 1993.
 442. Nakayama, H., S. Taneda, S. Kuwajima, S. Aoki, Y. Kuroda, K. Misawa, and S. Nakagawa. Production and characterization of antibodies to advanced glycation products on proteins. Biochem. Biophys. Res. Commun. 162: 740–745, 1989.
 443. Nanda, B. S., and R. Getty. Age‐related histomorphological changes in the cerebral arteries of domestic pig. Exp. Gerontol. 6: 453–460, 1971.
 444. Nejjar, I., M.‐T. Pieraggi, J. C. Thiers, and H. Bouissou. Age‐related changes in the elastic tissue of the human thoracic aorta. Atherosclerosis 80: 199–208, 1990.
 445. Neuberger, A., and H. G. B. Slack. The metabolism of collagen from liver, bone, skin and tendon in the normal rat. Biochem. J. 53: 47–52, 1953.
 446. Niedermuller, H., M. Skalicky, G. Hofecker, and A. Kment. Investigations on the kinetics of collagen‐metabolism in young and old rats. Exp. Gerontol. 12: 159–168, 1977.
 447. Nielsen, C. J., J. P. Bentley, and F. J. Marshall. Age‐related changes in reducible crosslinks of human dental pulp collagen. Arch. Oral. Biol. 28: 759–764, 1983.
 448. Nimni, M. E., E. Deguia, and L. A. Bavetta. Synthesis and turnover of collagen precursors in rabbit skin. Biochem. J. 102: 143–147, 1967.
 449. Nishimoto, S., M. Oimomi, and S. Baba. Glycation of collagen in the aorta and the development of aging. Clin. Chim. Acta 182: 235–238, 1989.
 450. Nishimoto, S. K., S. M. Padilla, and D. L. Snyder. The effect of food restriction and germ‐free environment on age‐related changes in bone matrix. J. Gerontol. 45: B164–B168, 1990.
 451. Nissen, R., G. J. Cardinale, and S. Udenfriend. Increased turnover of arterial collagen in hypertensive rats. Proc. Natl. Acad. Sci. USA 75: 451–453, 1978.
 452. Njoroge, F. G., and V. M. Monnier. The chemistry of the Maillard reaction under physiological conditions: a review. In: The Maillard Reaction in Aging, Diabetes and Nutrition, edited by J. W. Baynes and V. M. Monnier. New York: Alan R. Liss, 1989, p. 85–107.
 453. Njoroge, F. G., A. A. Fernandes, and V. M. Monnier. Mechanism of formation of the putative advanced glycosylation end product and protein crosslink 2‐(2‐furoyl)‐4(5)‐2(furanyl)1H‐imidazole. J. Biol. Chem. 263: 10646–10652, 1988.
 454. Njoroge, F. G., L. M. Sayre, V. M. Monnier. Detection of D‐glucose‐derived pyrrole compounds during Maillard reaction under physiological conditions. Carbohydr. Res. 167: 211–220, 1987.
 455. Nordmann, J. Au sujet du vieillissement du cristallin humain et de la pathogenie de la cataracte senile. Adv. Ophthalmol. 34: 1–73, 1977.
 456. Nordmann, J., and J. Klethi. L'activite Na‐K‐ATPasique dans le cristallin normal vieillissant et dans la cataracte senile. Arch. Ophthalmol. (Paris) 36: 523–552, 1976.
 457. Nordmann, J., H. Fink, and O. Hockwin. Die Wachstumskurve der menschlichen Linse. Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol. 191: 165–175, 1974.
 458. Nowack, H., S. Gay, G. Wick, U. Becker, and R. Timpl. Preparation and use in immunohistology of antibodies specific for type I and type III collagen and procollagen. J. Immunol. Methods 12: 117–124, 1976.
 459. Odetti, P., A. Borgoglio, A. de Pascale, R. Rolandi, and L. Adezati. Prevention of diabetes‐increased aging effect on rat collagen‐linked fluorescence by aminoguanidine and rutin. Diabetes 39: 796–801, 1990.
 460. Odetti, P., A. Borgoglio, and R. Rolandi. Age‐related increase of collagen fluorescence in human subcutaneous tissue. Metabolism 41: 655–658, 1992.
 461. Odetti, P., J. Fogarty, D. R. Sell, and V. M. Monnier. Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects. Diabetes 41: 153–159, 1992.
 462. Ogawa, T., T. Ono, M. Tsuda, and Y. Kawanishi. A novel fluorophore in insoluble collagen: a crosslinking moiety in collagen molecule. Biochem. Biophys. Res. Commun. 107: 1252–1257, 1982.
 463. Ohrloff, C. Age changes of enzyme properties in crystalline lens. Interdiscipl. Top. Gerontol. 12: 158–179, 1978.
 464. Ohrloff, C., O. Hockwin, R. Olson, and S. Dickman. Glutathione peroxidase, glutathione reductase and superoxide dismutase in the aging lens. Curr. Eye Res. 3: 109–111, 1984.
 465. Ohuchi, K., and S. Tsurufuji. Degradation and turnover of collagen in the mouse skin and the effect of whole body x‐irradiation. Biochim. Biophys. Acta 208: 475–481, 1970.
 466. Oimomi, M., Y. Maeda, F. Hata, Y. Kitamura, S. Matsumoto, H. Hatanaka, and S. Baba. A study of the age‐related acceleration of glycation of tissue proteins in rats. J. Gerontol. 43: B98–B104, 1988.
 467. Olczyk, K. Age‐related changes in collagen of human intervertebral discs. Gerontology. 38: 196–204, 1992.
 468. Oliver, C. N. Inactivation and oxidative modifications of proteins by stimulated neutrophils. Arch. Biochem. Biophys. 253: 62–67, 1987.
 469. Oliver, C. N., B. W. Ahn, M. E. Wittenberger, R. L. Levine, and E. R. Stadtman. Age‐related alterations of enzymes may involve mixed function oxidation reactions. In: Modern Aging Research: Modifications of Proteins During Aging, edited by R. C. Adelman, and E. R. Dekker. New York: Alan R. Liss, 1985, vol 7, p. 39–52.
 470. Olsen, G. G., and A. V. Everett. Retardation of the aging process in collagen fibers from the tail tendon of the old hypophysectomized rat. Nature 206: 307–308, 1965.
 471. Omerod, C. D., M. A. C. Edelstein, G. L. Schmidt, R. S. Jaurez, S. M. Finegold, and R. E. Smith. The intraocular environment and experimental anaerobic bacterial endophthalmitis. Arch. Ophthalmol. 105: 1571–1575, 1987.
 472. Ono, S., and M. Yamauchi. Collagen crosslinking of skin in patients with amyotrophic lateral sclerosis. Ann. Neurol. 31: 305–310, 1992.
 473. Oohira, A., and H. Nogami. Age‐related changes in physical and chemical properties of proteoglycans synthesized by costal and matrix‐induced cartilages in the rat. J. Biol. Chem. 255: 1346–1350, 1980.
 474. Ooshima, A., and Y. Yamori. Hypertension, vasculature and aging. Adv. Exp. Med. Biol. 129: 99–110, 1980.
 475. Ortwerth, B. J., and P. R. Olesen. Glutathione inhibits the glycation and crosslinking of lens proteins by ascorbic acid. Exp. Eye Res. 52: 439–444, 1988.
 476. Osborne‐Pellegrin, M. J., J. Farjanel, and W. Hornebeck. Role of elastase and lysyl oxidase activity in spontaneous rupture of internal elastic lamina in rats. Arteriosclerosis 10: 1136–1146, 1990.
 477. Palmer, W. G., and J. Papaconstantinou. Aging of α‐crystallins during development of the lens. Proc. Natl. Acad. Sci. USA 64: 404–408, 1969.
 478. Pande, A., W. H. Garner, and A. Spector. Glycosylation of human lens protein and cataractogenesis. Biochem. Biophys. Res. Commun. 89: 1260–1266, 1979.
 479. Patrick, J. S., S. R. Thorpe, and J. W. Baynes. Nonenzymatic glycosylation of protein does not increase with age in normal human lenses. J. Gerontol. 45: B18–B23, 1990.
 480. Pau, H., P. Graf, and H. Sies. Glutathione levels in human lens: regional distribution in different forms of cataract. Exp. Eye Res. 50: 17–20, 1990.
 481. Paulsson, M., M. Morgelin, H. Wiedemann, M. Beardmore‐Gray, D. Dunham, T. Hardingham, D. Heinegard, R. Timpl, and J. Engel. Extended and globular protein domains in cartilage proteoglycans. Biochem. J. 245: 763–772, 1987.
 482. Paz, M. A., D. A. Keith, and P. M. Gallop. Elastin isolation and cross‐linking. Methods Enzymol. 82: 571–587, 1982.
 483. Pearce, R. H., and B. J. Grimmer. Age and the chemical constitution of normal human dermis. J. Invest. Dermatol. 58: 347–361, 1972.
 484. Pearson, J. P., and R. M. Mason. Proteoglycan aggregates in adult human costal cartilage. Biochim. Biophys. Acta 583: 512–526, 1979.
 485. Perry, R. E., M. S. Swamy, and E. C. Abraham. Progressive changes in lens crystallin glycation and high molecular weight aggregate formation leading to cataract development in streptozocin‐diabetic rats. Exp. Eye Res. 44: 269–282, 1987.
 486. Piatigorsky, J. Lens crystallins: innovation associated with changes in gene regulation. J. Biol. Chem. 267: 4277–4280, 1992.
 487. Pierce, J. A., H. Resnick, and P. H. Henry. Collagen and elastin metabolism in the lungs, skin, and bones of adult rats. J. Lab. Clin. Med. 69: 485–492, 1967.
 488. Pietilä, K., and T. Nikkari. Role of the arterial smooth muscle cell in the pathogenesis of atherosclerosis. Med. Biol. 61: 31–44, 1983.
 489. Pirie, A. Glutathione peroxidase in lens and a source of hydrogen peroxide in aqueous humour. Biochem. J. 96: 244–253, 1965.
 490. Pirie, A. A light‐catalysed reaction in the aqueous humour of the eye. Nature 205: 500–501, 1965.
 491. Pirie, A. Color and solubility of the proteins of human cataracts. Invest. Ophthalmol. 7: 634–649, 1968.
 492. Plank, L., J. James, and C. A. Wagenvoort. Caliber and elastin content of the pulmonary trunk. Arch. Pathol. Lab. Med. 104: 238–241, 1980.
 493. Pongor, S., P. C. Ulrich, F. A. Bencsath, and A. Cerami. Aging of proteins: isolation and identification of a fluorescent chromophore from the reaction of polypeptides with glucose. Proc. Natl. Acad. Sci. USA 81: 2684–2688, 1984.
 494. Poole, A., R. Myllyla, J. C. Wagner, and R. C. Brown. Collagen biosynthesis enzymes in lung tissue and serum of rats with experimental silicosis. Br. J. Exp. Pathol. 66: 567–575, 1985.
 495. Porta, E. A., L. Keopuhiwa, N. S. Joun, and R. T. Nitta. Effects of the type of dietary fat at two levels of vitamin E in Wistar male rats during development and aging. III. Biochemical and morphometric parameters of the liver. Mech. Ageing Dev. 15: 297–335, 1981.
 496. Powell, J. T., N. Vine, and M. Crossman. On the accumulation of D‐aspartate in elastin and other proteins of the ageing aorta. Atherosclerosis 97: 201–208, 1992.
 497. Prabhakaram, M., and B. J. Ortwerth. The glycation‐associated crosslinking of lens proteins by ascorbic acid is not mediated by oxygen free radicals. Exp. Eye Res. 53: 261–268, 1991.
 498. Price, R. G., and R. G. Spiro. Studies on the metabolism of the renal glomerular basement membrane. J. Biol. Chem. 252: 8597–8602, 1977.
 499. Prockop, D. J., K. I. Kivirikko, L. Tuderman, and N. A. Guzman. The biosynthesis of collagen and its disorders. N. Engl. J. Med. 301: (Parts 1 and 2) 13–23, 77–85, 1979.
 500. Quaglino, D., Jr., R. Kennedy, C. Fornieri, L. Nanney, I. Pasquali, D. Ronchetti, and J. M. Davidson. Matrix gene expression during aging process revealed by in situ hybridization. J. Histochem. Cytochem. 37: 933, 1989.
 501. Quintarelu, G., E. Ippolito, and L. Roden. Age‐dependent changes on the state of aggregation of cartilage matrix. Lab. Invest. 32: 111–123, 1975.
 502. Radoff, S., Z. Makita, and H. Vlassara. Radioreceptor assay for advanced glycosylation endproducts. Diabetes 40: 1731–1738, 1991.
 503. Rafferty, N. S., and W. Goosens. Growth and aging of the lens capsule. Growth 42: 375–389, 1978.
 504. Rains, J. K., J. L. Bert, C. R. Roberts, and P. D. Pare. Mechanical properties of human tracheal cartilage. J. Appl. Physiol. 72: 219–225, 1992.
 505. Raju, K., and R. A. Anwar. Primary structures of bovine elastin a,b,c deduced from the sequences of cDNA clones. J. Biol. Chem. 262: 5755–5762, 1987.
 506. Ramirez, E., and M. Di Liberto. Complex and diversified regulatory programs control the expression of vertebrate collagen genes. FASEB J. 4: 1616–1623, 1990.
 507. Rao, G., and E. Cotlier. Free ε‐amino groups and 5‐hydroxy‐methyl‐furfuraldehyde content in clear and cataractous human lenses. Invest. Ophthalmol. 27: 98–102, 1986.
 508. Ratcliffe, A., J. A. Tyler, and T. E. Hardingham. Articular cartilage cultured with interleukin 1: increased release of link protein, hyaluronate‐binding region and other proteoglycan fragments. Biochem. J. 238: 571–580, 1986.
 509. Rathban, W. B., and D. C. Murray. Age‐related cysteine uptake as rate‐limiting in glutathione synthesis and glutathione half‐life in the cultured human lens. Exp. Eye Res. 53: 205–212, 1991.
 510. Reddy, V. N. Metabolism of glutathione in the lens. Exp. Eye Res. 11: 310–328, 1971.
 511. Reddy, V. N. Glutathione and its function in the lens—an overview. Exp. Eye Res. 50: 771–778, 1990.
 512. Reddy, V., F. J. Giblin, and H. Matsuda. Defense system of the lens against oxidative damage. In: Red Blood Cell and Lens Metabolism, edited by S. K. Srivastava. Amsterdam: Elsevier, 1980, p. 139–154.
 513. Reiser, K. M. Nonenzymatic glycation of collagen in aging and diabetes. Proc. Soc. Exp. Biol. Med. 196: 17–29, 1991.
 514. Reiser, K. M., M. A. Amigable, and J. A. Last. Nonenzymatic glycation of type I collagen: the effects of aging on preferential glycation sites. J. Biol. Chem. 267: 24207–24216, 1992.
 515. Reiser, K. M., S. M. Hennessy, and J. A. Last. Analysis of age‐associated changes in collagen crosslinking in the skin and lung in monkeys and rats. Biochim. Biophys. Acta 926: 339–348, 1987.
 516. Reiser, K., R. J. McCormick, and R. B. Rucker. Enzymatic and nonenzymatic crosslinking of collagen and elastin. FASEB J. 6: 2439–2449, 1992.
 517. Ricard‐Blum, S., and G. Ville. Collagen crosslinking. Cell. Mol. Biol. 34: 581–590, 1988.
 518. Richard, S., C. Tamas, D. R. Sell, and V. M. Monnier. Tissue‐specific effects of aldose reductase inhibition on fluorescence and cross‐linking of extracellular matrix in chronic galactosemia. Diabetes 40: 1049–1056, 1991.
 519. Richey, M. L., H. K. Richey, and N. A. Fenske. Aging‐related skin changes: development and clinical meaning. Geriatrics 43: 49–64, 1988.
 520. Robert, L. Aging of connective tissue. Mech. Ageing Dev. 14: 273–282, 1980.
 521. Robert, L. Aging of connective tissues. Experientia 37: 1055–1058, 1981.
 522. Robert, L. and W. Hornebeck (Eds). Elastin and Elastasis. Boca Raton, FL: CRC Press, 1989.
 523. Robert, L., M. P. Jacob, C. Frances, G. Godeau, and W. Hornebeck. Interaction between elastin and elastases and its role in the aging of the arterial wall, skin and other connective tissues. A review. Mech. Ageing Dev. 28: 155–166, 1984.
 524. Roberts, C. R., J. S. Mort, and P. J. Roughley. Treatment of cartilage proteoglycan aggregate with hydrogen peroxide: relationship between observed degradation products and those that occur naturally during aging. Biochem. J. 247: 349–357, 1987.
 525. Robins, S. P. Analysis of the crosslinking components in collagen and elastin. Methods Biochem. Anal. 28: 329–379, 1982.
 526. Robins, S. P., and A. J. Bailey. Age‐related changes in collagen: the identification of reducible lysine‐carbohydrate condensation products. Biochem. Biophys. Res. Commun. 48: 76–84, 1972.
 527. Robins, S. P., and A. J. Bailey. The chemistry of the collagen crosslinks: the mechanism of stabilization of the reducible intermediate cross‐links. Biochem. J. 149: 381–385, 1975.
 528. Robins, S. P., and A. Duncan. Cross‐linking of collagen: location of pyridinoline in bovine articular cartilage at two sites of the molecule. Biochem. J. 215: 175–182, 1983.
 529. Robins, S. P., M. Shimokomaki, and A. J. Bailey. The chemistry of the collagen cross‐links: age‐related changes in the reducible components of intact bovine collagen fibers. Biochem. J. 131: 771–780, 1973.
 530. Rodriguez‐Caballero, M. L., J. P. Gerhard, and J. Nordmann. L'epaisseur cortical du cristallin humain. Doc. Ophthalmol. 35: 287–295, 1973.
 531. Rodriguez‐Martinez, M. A., and A. Ruiz‐Torres. Homeostasis between lipid peroxidation and antioxidant enzyme activities in healthy human aging. Mech. Ageing Dev. 66: 213–222, 1992.
 532. Rogozinski, S., G. O. Blumenfeld, and S. Seifter. The nonenzymatic glycosylation of collagen. Arch. Biochem. Biophys. 221: 428–437, 1983.
 533. Romero‐Chapman, N., J. Lee, D. Tinker, J. Y. Uriu‐Hare, C. L. Keen, and R. R. Rucker. Purification, properties and influence of dietary copper on accumulation and functional activity of lysyl oxidase in rat skin. Biochem. J. 275: 657–662, 1991.
 534. Rosenberg, L. C., H. U. Choi, L.‐H. Tang, T. L. Johnson, S. Pal, C. Webber, A. Reiner, and A. R. Poole. Isolation of dermatan sulfate proteoglycans from mature bovine articular cartilages. J. Biol. Chem. 260: 6304–6313, 1985.
 535. Rosenbloom, J. Elastin: biosynthesis, structure, degradation and role in disease processes. Connect. Tissue Res. 10: 73–91, 1982.
 536. Rosenbloom, J., W. R. Abrams, and R. Mecham. Extracellular matrix 4: the elastic fiber. FASEB J. 7: 1208–1218, 1993.
 537. Ross, W. M., M. O. Creighton, J. R. Trevithick, P. J. Sterat‐Detlaan, and M. Sanwal. Modelling cataractogenesis: VI. Induction by glucose in vitro or in diabetic rats: prevention and reversal by glutathione. Exp. Eye Res. 37: 559–573, 1983.
 538. Roughley, P. J. Changes in cartilage proteoglycan structure during ageing: origin and effects—a review. Agents Actions [Suppl.] 18: 19–29, 1986.
 539. Roughley, P. J. Structural changes in the proteoglycans of human articular cartilage during aging. J. Rheumatol. 14 (suppl): 14–15, 1987.
 540. Roughley, P. J., and J. S. Mort. Ageing and the aggregating proteoglycans of human articular cartilage. Clin. Sci. 71: 337–344, 1986.
 541. Roughley, P. J., and R. J. White. Age‐related changes in the structure of the proteoglycan subunits from human articular cartilage. J. Biol. Chem. 255: 217–224, 1980.
 542. Roughley, P. J., Q. Nguyen, and J. S. Mort. Mechanisms of proteoglycan degradation in human articular cartilage. J. Rheumatol. [Suppl.] 27: 52–54, 1991.
 543. Roughley, P. J., R. J. White, A. R. Poole, and J. S. Mort. The inability to prepare high‐buoyant density proteoglycan aggregates from extracts of normal adult human articular cartilage. Biochem. J. 221: 637–644, 1984.
 544. Roy, D. Age‐dependent changes in the abundance of the major polypeptides of human lens membrane. Biochem. Biophys. Res. Commun. 88: 30–36, 1979.
 545. Roy, D., and A. Spector. Human insoluble lens protein. I. Separation and partial characterization of polypeptides. Exp. Eye Res. 26: 429–443, 1978.
 546. Roy, D., and A. Spector. Human insoluble lens protein II. Isolation and characterization of a 9600 dalton polypeptide. Exp. Eye Res. 26: 445–459, 1978.
 547. Roy, D., J. Dillon, E. Wada, W. Chaney, and A. Spector. Nondisulfide polymerization of ‐γ‐ and β‐crystallins in the human lens. Proc. Natl. Acad. Sci. USA 81: 2878–2881, 1984.
 548. Rucker, R. B., and D. Tinker. Structure and metabolism of arterial elastin. Int. Rev. Exp. Pathol. 17: 1–47, 1977.
 549. Ruckudge, G. J., G. Milne, B. A. McGaw, E. Milne, and S. P. Robins. Turnover rates of different collagen types measured by isotope ratio mass spectrometry. Biochim. Biophys. Acta 1156: 57–61, 1992.
 550. Ruoslahti, E. Structure and biology of proteoglycans. Annu. Rev. Cell Biol. 4: 229–255, 1988.
 551. Russel, P., S. G. Smith, D. A. Carper, and J. H. Kinoshita. Age‐ and cataract‐related changes in the heavy molecular weight proteins and gamma crystallin composition of the mouse lens. Exp. Eye Res. 29: 245–255, 1979.
 552. Said, F. S., and R. A. Weale. The variation with age of the spectral transmissivity of the living human crystalline lens. Gerontologia 3: 213–231, 1959.
 553. Saito, S., Y. Takahashi, M. Wyman, and P. F. Kador. Progression of sugar cataract in the dog. Invest. Ophthalmol. Vis. Sci. 32: 1925–1931, 1991.
 554. Samila, Z. J., and S. A. Carter. The effect of aging on the unfolding of elastin lamellae and collagen fibers with stretch in human cartoid arteries. Can. J. Physiol. Pharmacol. 59: 1050–1057, 1981.
 555. Sampaio, L. de O., M. T. Bayliss, T. E. Hardingham, and H. Muir. Dermatan sulphate proteoglycan from human articular cartilage. Biochem. J. 254: 757–764, 1988.
 556. Sanada, H., J. Shikata, H. Hamamoto, Y. Ueba, T. Yamamura, and T. Takeda. Changes in collagen cross‐linking and lysyl oxidase by estrogen. Biochim. Biophys. Acta 541: 408–413, 1978.
 557. Sandberg, H. O., and O. Closs. The alpha and gamma crystallin content in aqueous humor of eyes with clear lenses and with cataracts. Exp. Eye Res. 28: 601–610, 1979.
 558. Sasaki, R., S. Ichikawa, H. Yamagiwa, A. Ito, and S. Yamagata. Aging and hydroxyproline content in human heart muscle. Tohoku J. Exp. Med. 118: 11–16, 1976.
 559. Satoh, K. Age‐related changes in the structural proteins of human lens. Exp. Eye Res. 14: 53–57, 1972.
 560. Satoh, K., M. Bando, and A. Nakajima. Fluorescence in human lens. Exp. Eye Res. 16: 167–172, 1973.
 561. Schaub, M. C. Qualitative and quantitative changes of collagen in parenchymatous organs of the rat during ageing. Gerontologia 8: 114–122, 1963.
 562. Schleicher, E., and O. H. Wieland. Kinetic analysis of glycation as a tool for assessing the half‐life of proteins. Biochim. Biophys. Acta 884: 199–205, 1986.
 563. Schmidt, A. M., M. Vianna, M. Gerlach, J. Brett, J. Ryan, J. Kao, C. Esposito, H. Hegarty, W. Hurley, M. Clauss, F. Wang, Y.‐C. E. Pan, T. C. Tsang, and D. Stern. Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J. Biol. Chem. 267: 14987–14997, 1992.
 564. Schoenmakers, J. J. G., J. J. T. Gerding, and H. Bloemendal. The secondary structure of α‐crystallin. Eur. J. Biochem. 11: 472–480, 1969.
 565. Scott, J. E. Proteoglycan: collagen interactions and subfibrillar structure in collagen fibrils. Implications in the development and ageing of connective tissues. J. Anat. 169: 23–35, 1990.
 566. Scott, J. E., R.‐G. Qian, W. Henkel, and R. W. Glanville. An Ehrlich chromogen in collagen cross‐links. Biochem. J. 209: 263–264, 1983.
 567. Sebag, J. Ageing of the vitreous. Eye 1: 254–262, 1987.
 568. Sell, D. R., and V. M. Monnier. Isolation, purification and partial characterization of novel fluorophores from aging human insoluble collagen‐rich tissue. Connect. Tissue Res. 19: 77–92, 1989.
 569. Sell, D. R., and V. M. Monnier. Structure elucidation of a senescence cross‐link from human extracellular matrix: implication of pentoses in the aging process. J. Biol. Chem. 264: 21597–21602, 1989.
 570. Sell, D. R., and V. M. Monnier. End‐stage renal disease and diabetes catalyze the formation of a pentose‐derived crosslink from aging human collagen. J. Clin. Invest. 85: 380–384, 1990.
 571. Sell, D. R., E. C. Carlson, and V. M. Monnier. Differential effects of type 2 (non‐insulin‐dependent) diabetes mellitus on pentosidine formation in skin and glomerular basement membrane. Diabetologia 36: 936–941, 1993.
 572. Sell, D. R., A. Lapolla, P. Odetti, J. Fogarty, and V. M. Monnier. Pentosidine formation in skin correlates with severity of complications in individuals with long‐standing IDDM. Diabetes 41: 1286–1292, 1992.
 573. Sell, D. R., R. H. Nagaraj, S. K. Grandhee, P. Odetti, A. Lapolla, J. Fogarty, and V. M. Monnier. Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging, and uremia. Diabetes Metab. Rev. 7: 239–251, 1991.
 574. Sephel, G. C., and J. M. Davidson. Elastin production in human skin fibroblast cultures and its decline with age. J. Invest. Dermatol. 86: 279–285, 1986.
 575. Shapiro, S. D., S. K. Endicott, M. A. Province, J. A. Pierce, and E. J. Campbell. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D‐aspartate and nuclear weapons‐related radiocarbon. J. Clin. Invest. 87: 1828–1834, 1991.
 576. Shikata, H., M. Hiramatsu, T. Masumizu, D. Fujimoto, and N. Utsumi. Age‐related changes in the content of non‐reducible crosslinks in rat mandibular bone. Arch. Oral. Biol. 30: 451–453, 1985.
 577. Shilton, B. H., and D. J. Walton. Sites of glycation of human and horse liver alcohol dehydrogenase in vivo. J. Biol. Chem. 266: 5587–5592, 1991.
 578. Shimizu, K., T. Furuya, Y. Takeo, K. Shirama, and K. Maekawa. Decrease of collagen content in the intraocular fluid of senile rats. Acta Anat. 109: 44–46, 1981.
 579. Shin, D. B., and M. S. Feather. 3‐deoxy‐l‐glycero‐pentos‐2‐ulose (3‐deoxy‐l‐xylosone) and l‐threo‐pentosulose (l‐xylosone) as intermediates in the degradation of l‐ascorbic acid. Carbohydr. Res. 208: 246–250, 1990.
 580. Shuster, S., M. M. Black, and E. McVitie. The influence of age and sex on skin thickness, skin collagen and density. Br. J. Dermatol. 93: 639–643, 1975.
 581. Shuster, S., E. J. Raffle, and E. Bottoms. Skin collagen in rheumatoid arthritis, and the effect of corticosteroids. Lancet 1: 525–527, 1967.
 582. Siebinga, S., G. F. J. M. Vrensen, F. F. M. De Mal, and J. Greve. Age‐related change in local water and protein content of human eye lenses measured by Raman microspectroscopy. Exp. Eye Res. 53: 233–239, 1991.
 583. Silbermann, M., K. von der Mark, M. van Menxel, and A. Z. Reznick. Effect of short‐term physical stress on DNA and collagen synthesis in the femur of young and old mice. Gerontology 33: 49–56, 1987.
 584. Sippel, T. O. Energy metabolism in the lens during aging. Invest. Ophthalmol. Vis. Sci. 4: 502–513, 1965.
 585. Smalley, J. W. Age‐related changes in hydroxylysylglycosides of human glomerular basement membrane collagen. Exp. Gerontol. 15: 65–66, 1980.
 586. Smith, J. B., G. A. Shun‐Shin, L. J. Miesbauer, and D. L. Smith. Posttranslational modifications of the water soluble α‐crystallins from renal failure patients. Invest. Ophthalmol. 34: 1341, 1993.
 587. Smith, P. R., and P. J. Thornalley. Mechanism of the degradation of non‐enzymatically glycated proteins under physiological conditions: studies with the model fructosamine, Nε‐(1‐deoxy‐D‐fructos‐1‐yl) hippuryl‐lysine. Eur. J. Biochem. 210: 729–739, 1992.
 588. Smith, P. R., H. H. Somani, P. J. Thornalley, J. Benn, and P. H. Sonksen. Evidence against the formation of 2‐amino‐6‐(2‐formyl‐5‐hydroxymethyl‐pyrrol‐l‐yl)‐hexanoic acid (“pyrraline”) as an early‐stage product or advanced glycation end product in non‐enzymic protein glycation. Clin. Sci. 84: 87–93, 1993.
 589. Snowden, J. M., D. R. Eyre, and D. A. Swann. Vitreous structure. VI. Age‐related changes in the thermal stability and crosslinks of vitreous, articular cartilage and tendon collagens. Biochim. Biophys. Acta 706: 153–157, 1982.
 590. Sobel, H. Ageing and age‐associated disease. Lancet II: 1191–1192, 1970.
 591. Sobin, S. S. Landis Award lecture. Questions and signposts in microvascular research. Microvasc. Res. 21: 1–18, 1981.
 592. Spector, A. Aggregation of α‐crystallin and its possible relationship to cataract formation, Isr. J. Med. Sci. 8: 1577–1582, 1972.
 593. Spector, A., Aging of the lens and cataract formation. In: Aging and Human Visual Function, edited by R. Sekuler, D. Kline and K. Dismukes. New York: Alan R. Liss, 1982, p. 27–43.
 594. Spector, A., The lens and oxidative stress. In: Oxidative Stress. Oxidants and Antioxidants, edited by H. Sies. London: Academic Press, 1991, p. 529–558.
 595. Spector, A., and W. H. Garner. Hydrogen peroxide and human cataract. Exp. Eye Res. 33: 673–681, 1981.
 596. Spector, A., R. Chiesa, J. Sredy, and W. Garner. CAMP‐dependent phosphorylation of bovine lens α‐crystallin. Proc. Natl. Acad. Sci. USA 82: 4712–4716, 1985.
 597. Spector, A., M. H. Garner, W. H. Garner, D. Roy, P. Farnsworth, and S. Shyne. An extrinsic membrane polypeptide associated with high‐molecular aggregates in human cataract. Science 204: 1323–1326, 1978.
 598. Spector, A., S. Li, and J. Sigelman. Age‐dependent changes in the molecular size of human lens proteins and their relationship to light scatter. Invest. Ophthalmol. 13: 795–798, 1974.
 599. Spina, M., and G. Garbin. Age‐related chemical changes in human elastins from non‐atherosclerotic areas of thoracic aorta. Atherosclerosis 24: 267–279, 1976.
 600. Spina, M., S. Garbisa, J. Hinnie, and J. C. Hunter, A. Serafini‐Fracassini. Age‐related changes in composition and mechanical properties of the tunica media of the upper thoracic human aorta. Arteriosclerosis 3: 64–76, 1983.
 601. Srivastava, O. P. Age‐related increase in concentration and aggregation of degraded polypeptides in human lenses. Exp. Eye Res. 47: 525–543, 1988.
 602. Srivastava, S. K. and E. Beutler. Cleavage of lens protein‐GSH mixed disulfide by GSH reductase. Exp. Eye Res. 17: 33–42, 1973.
 603. Stanescu, V., F. Chaminade, and M.‐P. Muriel. Age‐related changes in small proteoglycans of low buoyant density of human articular cartilage. Connect. Tissue Res. 17: 239–252, 1988.
 604. Starcher, B. C., and R. P. Mecham. Desmosine radioimmunoassay as a means of studying elastogenesis in cell culture. Connect. Tissue Res. 8: 255–258, 1981.
 605. Starcher, B. C., S. M. Partridge, and D. F. Elsden. Isolation and partial characterization of a new amino acid from reduced elastin. Biochemistry 6: 2425–2432, 1967.
 606. Stevens, V. J., C. A. Rouzer, V. M. Monnier, and A. Cerami. Diabetic cataract formation: potential role of glycosylation of lens crystallins. Proc. Natl. Acad. Sci. USA 75: 2918–2922, 1978.
 607. Stidworthy, G., Y. F. Masters, and M. R. Shetlar. The effect of aging on mucopolysaccharide composition of human costal cartilage as measured by hexosamine and uronic acid content. J. Gerontol. 13: 10–13, 1958.
 608. Stone, P. J., C. Franzblau, and H. M. Kagan. Proteolysis of insoluble elastin. Methods Enzymol. 82: 588–605, 1982.
 609. Strehler, B. L., Definitions, criteria, categories, and origins of age changes. In: Time, Cells, Aging, (2nd Ed.) edited by B. L. Strehler. New York: Academic Press, 1977, p. 5–30.
 610. Stricklin, G. P., and M. S. Hibbs. Biochemistry and physiology of mammalian collagenases. In: Collagen, edited by M. E. Nimni. Boca Raton, FL: CRC Press, 1988, vol. I, p. 187–205.
 611. Stuhlsatz, H. W., H. Loffler, V. Mohanaradhakrishnan, S. Cosma, and H. Greiling. Topographic and age‐ dependent distribution of the glycosaminoglycans in human aorta. J. Clin. Chem. Clin. Biochem. 20: 713–721, 1982.
 612. Sundholm, F., A. Visapää, and J. Björksten. Cross‐linking of collagen in the presence of oxidizing lipid. Lipids 13: 755–757, 1978.
 613. Swamy, M. S., and E. C. Abraham. Lens protein composition, glycation and high molecular weight aggregation in aging rats. Invest. Ophthalmol. Vis. Sci. 28: 1693–1701, 1987.
 614. Swamy, M. S., A. Abraham, and E. C. Baraham. Glycation of human lens proteins. Preferential glycation of αA subunits. Exp. Eye Res. 54: 337–345, 1992.
 615. Sweet, M. B. E., E. J.‐M. A. Thonar, and J. Marsh. Age‐related changes in proteoglycan structure. Arch. Biochem. Biophys. 198: 439–448, 1979.
 616. Takata, K., S. Horiuchi, N. Araki, M. Shiga, M. Saitoh, and Y. Morino. Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde‐modified proteins. J. Biol. Chem. 263: 14819–14825, 1988.
 617. Takeda, K., A. Gosiewska, and B. Peterkofsky. Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts. J. Cell Physiol. 153: 450–459, 1992.
 618. Takemoto, L., and P. Azari. Amino acid composition of normal and cataractous human lens protein. Exp. Eye Res. 23: 1–7, 1976.
 619. Takemoto, L., and M. Takehana. Major intrinsic polypeptide (MIP 26K) from human lens membrane: characterization of low‐ molecular weight forms in the aging human lens. Exp. Eye Res. 43: 661–667, 1986.
 620. Takemoto, L., T. Kodama, and D. Takemoto. Covalent changes at the N‐ and C‐terminal regions of ‐γ‐crystallins during aging of the normal human lens. Exp. Eye Res. 45: 207–274, 1987.
 621. Tang, S.‐S., P. C. Trackman, and H. M. Kagan. Reaction of aortic lysyl oxidase with β‐aminopropionitrile. J. Biol. Chem. 258: 4331–4338, 1983.
 622. Tao, R. V., Y. Takahashi, and P. F. Kador. Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. Invest. Ophthalmol. Vis. Sci. 32: 1630–1637, 1991.
 623. Taylor, A., and K. J. A. Davies. Protein oxidation and loss of protease activity may lead to cataract formation in the aged lens. Free Radic. Biol. Med. 3: 371–377, 1987.
 624. Taylor, A., J. H. Jahngen, J. Blondin, and E. G. E. Jahngen, Jr.. Ascorbate delays ultraviolet‐induced, age‐related damage to lens protease and the effect of maturation and aging on the function of the ubiquitin‐lens protein conjugating apparatus. Proteases Biol. Control Biotech. 57: 283–293, 1987.
 625. Taylor, H. R., S. K. West, F. S. Rosenthal, B. Munoz, H. S. Newland, H. Abbey, and E. A. Emmett. Effect of ultraviolet radiation on cataract formation. N. Engl. J. Med. 319: 1429–1433, 1988.
 626. Taylor, J. R., J. E. Scott, A. M. Cribb, and T. R. Bosworth. Human intervertebral disc acid glycosaminoglycans. J. Anat. 180: 137–141, 1992.
 627. Testa, M., C. Fiore, N. Bocci, and S. Calabro. Effect of the oxidation of sulfhydryl groups on lens proteins. Exp. Eye Res. 7: 276–290, 1968.
 628. Theocharis, D. A. Comparisons between extracted and residual proteoglycans on the glycosaminoglycan level and changes with ageing. Int. J. Biochem. 17: 155–160, 1985.
 629. Thomas, D. P., R. J. McCormick, S. D. Zimmerman, R. K. Vadlamudi, and L. E. Gosselin. Aging‐ and training‐induced alterations in collagen characteristics of rat ventricle and papillary muscle. Am. J. Physiol. 263: H778–H783, 1992.
 630. Thompson, R. C., and J. E. Ballou. Studies of metabolic turnover with tritium as a tracer. V. The predominantly nondynamic state of body constituents in the rat. J. Biol. Chem. 223: 795–809, 1956.
 631. Thonar, E. J.‐M. A., and M. B. E. Sweet. Maturation‐related changes in proteoglycans of fetal articular cartilage. Arch. Biochem. Biophys. 208: 535–547, 1981.
 632. Thonar, E. J.‐M. A., S. Bjornsson, and K. E. Kuettner. Age‐related changes in cartilage proteoglycans. In: Articular Cartilage Biochemistry, edited by K. Kuettner, R. Schleyerbach and V. C. Hascall. New York: Raven Press, 1986, p. 273–288.
 633. Tilson, M. D. Further studies of a putative cross‐linking amino acid (3‐deoxypyridinoline) in skin from patients with abdominal aortic aneurysms. Surgery 98: 888–891, 1985.
 634. Tinker, D. H., and A. L. Tappel. A partial characterization of the major fluorophore of bovine ligamentum elastin. Connect. Tissue Res. 11: 309–319, 1983.
 635. Tinker, D. H., R. B. Rucker, and A. L. Tappel. Variation of elastin fluorescence with method of preparation: determination of the major fluorophore of fibrillar elastin. Connect. Tissue Res. 11: 299–308, 1983.
 636. Tobari, I. Aging and eye diseases II. Nippon Ganka Gakkai Zasshi. 47: 341–344, 1976.
 637. Tomoda, K., S. Morii, T. Yamashita, and T. Kumazawa. Histologic architecture of submucosal connective tissues in human eustachian tube with supplemental reference to the effects of aging. Arch. Otorhinolaryngol. 232: 57–63, 1981.
 638. Triphaus, G. F., A. Schmidt, and E. Buddecke. Age‐related changes in the incorporation of [35S] sulfate into two proteoglycan populations from human cartilage. Hoppe Seylers Z. Physiol. Chem. 361: 1773–1779, 1980.
 639. Truscott, R. J. W., and R. C. Augusteyn. Oxidative changes in human lens proteins during senile nuclear cataract formation. Biochim. Biophys. Acta 492: 43–52, 1977.
 640. Truscott, R. J. W., and R. C. Augusteyn. The state of sulfhydryl groups in normal and cataractous human lenses. Exp. Eye Res. 25: 139–148, 1977.
 641. Truscott, R. J. W., and R. C. Augusteyn. Changes in human lens proteins during nuclear cataract formation. Exp. Eye Res. 24: 159–170, 1977.
 642. Truscott, R. J. W., K. Fuall, and R. C. Augusteyn. The identification of anthranilic acid in proteolytic digest of cataractous lens proteins. Ophthalmic Res. 9: 263–268, 1977.
 643. Tsujl, T., and T. Hamada. Age‐related changes in human dermal elastic fibers. Br. J. Dermatol. 105: 57–63, 1981.
 644. Tuderman, L., and K. I. Kivirikko. Immunoreactive prolyl hydroxylase in human skin, serum and synovial fluid: changes in the content and components with age. Eur. J. Clin. Invest. 7: 295–299, 1977.
 645. Uchiyama, A., T. Inoue, and D. Fujimoto. Synthesis of pyridinoline during in vitro aging of bone collagen. J. Biochem. (Tokyo) 90: 1795–1798, 1981.
 646. Uchiyama, A., T. Ohishi, M. Takahashi, K. Kushida, T. Inoue, M. Fujie, and K. Horiuchi. Fluorophores from aging human articular cartilage. J. Biochem. 110: 714–718, 1991.
 647. Uitto, J. Connective tissue biochemistry of the aging dermis. Clin. Geriatr. Med. 5: 127–147, 1989.
 648. Uitto, J., M. J. Fazio, and D. R. Olsen. Molecular mechanisms of cutaneous aging. J. Am. Acad. Dermatol. 21: 614–622, 1989.
 649. Urban, J. P. G., and J. F. McMullin. Swelling pressure of the intervertebral disc: influence of proteoglycan and collagen contents. Biorheology 22: 145–157, 1985.
 650. Vailas, A. C., V. A. Pedrini, A. Pedrini‐Mille, and J. O. Holloszy. Patellar tendon matrix changes associated with aging and voluntary exercise. J. Appl. Physiol. 58: 1572–1576, 1985.
 651. van Boekel, M. A. M., and J. Hoenders. Glycation‐induced crosslinking of calf‐lens crystallins. Exp. Eye Res. 52: 90–94, 1991.
 652. van den Oetelaar, P. J. M., and H. J. Hoenders. Racemizaton of aspartyl residues in proteins from normal and cataractous human lenses: an aging process without involvement in cataract formation. Exp. Eye Res. 48: 209–214, 1989.
 653. van der Ouderaa, F. J., W. W. de Jong, A. Hilderink, and H. Bloemendal. The amino acid sequence of the αB2 chain of bovine α‐crystallin. Eur. J. Biochem. 49: 157–168, 1984.
 654. van der Rest, M., and P. Bruckner. Collagens: diversity at the molecular and supramolecular levels. Curr. Opinion Struct. Biol. 3: 430–436, 1993.
 655. van der Rest, M., and R. Garrone. Collagen family of proteins. FASEB J. 5: 2814–2823, 1991.
 656. van Haard, P. M. M., J. A. Kramps, H. J. Hoenders, and J. Wollensak. Development of nondisulfide covalent crosslinks in nuclear cataractogenesis. Interdiscipl. Top. Gerontol. 13: 212–224, 1978.
 657. van Heyningen, R., The lens: metabolism and cataract. In: The Eye (2nd ed.), edited by H. Davson. New York: Academic Press, 1969, vol. 1, p. 381–488.
 658. van Heyningen, R. Fluorescent glucoside in the human lens. Nature 230: 393–394, 1971.
 659. van Heyningen, R. Assay of fluorescent glucosides in the human lens. Exp. Eye Res. 15: 121–126, 1973.
 660. van Heyningen, R., The glucoside of 3‐hydroxykynurenine and other fluorescent compounds in the human lens. In: The Human Lens—In Relation to Cataract, edited by B. T. Philipson and P. P. Fagerholm. Amsterdam: Elsevier, 1973, p. 151–171.
 661. van Kleef, F. S. M., W. W. de Jong, and H. J. Hoenders. Stepwise degradations and deamination of the eye lens protein α‐crystallin in aging. Nature 258: 264–266, 1975.
 662. van Kleef, S. M., W. Willems‐Thijssen, and H. J. Hoenders. Intracellular degradation and deamidation of alpha‐crystallin subunits. Eur. J. Biochem. 66: 477–483, 1976.
 663. Varma, S. D., N. A. Beachy, and R. D. Richards. Photoperoxidation of lens lipids: prevention by vitamin E. Photochem. Photobiol. 36: 623–626, 1982.
 664. Varma, S. D., D. Chand, Y. R. Sharma, J. F. Kuck, Jr., and R. D. Richards. Oxidative stress on lens cataract formation: role of light and oxygen. Curr. Eye Res. 3: 35–57, 1984.
 665. Varma, S. D., S. Kumar, and R. D. Richards. Light‐induced damage to ocular lens cation pump: prevention by vitamin C. Proc. Natl. Acad. Sci. USA 76: 3504–3506, 1979.
 666. Varma, S. D., V. K. Srivastava, and R. D. Richards. Photoperoxidation in lens and cataract formation: preventative role of superoxide dismutase, catalase and vitamin C. Ophthalmic Res. 14: 167–175, 1982.
 667. Vasan, N. S., R. A. Saporito, Jr., S. Savaswathi, J. V. Tesoriero, and S. Manley. Alterations of renal cortex and medullary glycosaminoglycans in aging dog kidney. Biochim. Biophys. Acta 760: 197–205, 1983.
 668. Verzár, F. Veranderungen der thermoelastichen Knontrakfion der Sehnenfasern im Alter. Helv. Physiol. Pharmacol. Acta. 13: C64, 1955.
 669. Verzár, F. The aging of collagen. Sci. Am. 208: 104–114, April 1963.
 670. Vishwanath, V., K. E. Frank, C. A. Elmets, P. J. Dauchot, and V. M. Monnier. Glycation of skin collagen in type I diabetes mellitus: correlation with long‐term complications. Diabetes 35: 916–921, 1986.
 671. Vlassara, H., M. Brownlee, and A. Cerami. High‐affinity receptor‐mediated uptake and degradation of glucose‐modified proteins: a potential mechanism for the removal of senescent macromolecules. Proc. Natl. Acad. Sci. USA 82: 5588–5592, 1985.
 672. Vlassara, H., M. Brownlee, and A. Cerami. Macrophage receptor‐mediated processing and regulation of advanced glycosylation endproduct (AGE)‐modified proteins: role in aging and diabetes. In: The Maillard Reaction in Aging, Diabetes and Nutrition, edited by. J. W. Baynes and V. M. Monnier. New York: Alan R. Liss, 1989, p. 205–218.
 673. Vlassara, H., H. Fuh, Z. Makita, S. Krungkrai, A. Cerami, and R. Bucala. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc. Natl. Acad. Sci. USA 89: 12043–12047, 1992.
 674. Vogel, H. G. Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats. Mech. Ageing Dev. 14: 283–292, 1980.
 675. Vogel, H. G., Mechanical properties of rat skin with aging. In: Aging and the Skin, edited by A. K. Balin and A. M. Kligman. New York: Raven Press, 1989, p. 227–275.
 676. Vogel, H. G. Species differences of elastic and collagenous tissue—influence of maturation and age. Mech. Ageing Dev. 57: 15–24, 1991.
 677. Voorter, C. E. M., W. A. DeHaard‐Hoehman, P. J. M. Oetelaar, H. Bloemendal, and W. W. De Jong. Spontaneous peptide bond cleavage in aging α‐crystallin through a succinimide intermediate. J. Biol. Chem. 263: 19020–19023, 1988.
 678. Walters, C., and D. R. Eyre. Collagen crosslinks in human dentin: increasing content of hydroxypyridinium residues with age. Calcif. Tissue Int. 35: 401–405, 1983.
 679. Warren, R., V. Gartstein, A. M. Kligman, W. Montagna, R. A. Allendorf, and G. M. Ridder. Age, sunlight, and facial skin: a histologic and quantitative study. J. Am. Acad. Dermatol. 25: 751–760, 1991.
 680. Weiter, J. J. and E. D. Finch. Paramagnetic species in cataractous human lenses. Nature 254: 536–537, 1975.
 681. West, M. D., O. M. Pereira‐Smith, and J. R. Smith. Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity. Exp. Cell Res. 184: 138–147, 1989.
 682. Willen, M. D., J. M. Sorrell, C. C. Lekan, B. R. Davis, and A. I. Caplan. Patterns of glycosaminoglycan proteoglycan immunostaining in human skin during aging. J. Invest. Dermatol. 96: 968–974, 1991.
 683. Wolf, B., A. M. Gressner, Z. Nevo, and H. Greiling. Age‐related decrease in the activity of UDP‐xylose: core protein xylosyltransferase in rat costal cartilage. Mech. Ageing Dev. 19: 181–190, 1982.
 684. Wolff, S. P., and R. T. Dean. Glucose autoxidation and protein modification: the potential role of autoxidative glycosylation in diabetes. Biochem. J. 245: 243–250, 1987.
 685. Wolff, S. P., Z. A. Bascal, and J. V. Hunt. Autoxidative glycosylation: free radicals and glycation theory. In: Maillard Reaction in Aging, Diabetes, and Nutrition, edited by J. W. Baynes and V. M. Monnier. New York: Alan R. Liss, 1989, p. 259–275.
 686. Yamauchi, M., and G. L. Mechanic. Cross‐linking of collagen. In: Collagen, edited by M. E. Nimni. Boca Raton, FL: CRC Press, 1988, vol. I, p. 157–172.
 687. Yamauchi, M., R. E. London, C. Guenat, F. Hashimoto, and G. L. Mechanic. Structure and formation of a stable histidine‐based trifunctional cross‐link in skin collagen. J. Biol. Chem. 262: 11428–11434, 1987.
 688. Yamauchi, M., D. T. Woodley, and G. L. Mechanic. Aging and cross‐linking of skin collagen. Biochem. Biophys. Res. Commun. 152: 898–903, 1988.
 689. Ylä‐Herttuala, S., H. Sumuvuori, K. Karkola, M. Möttönen, and T. Nikkari. Glycosaminoglycans in normal atherosclerotic human coronary arteries. Lab. Invest. 54: 402–407, 1986.
 690. Young, R. W. Age‐Related Cataract. New York: Oxford University Press, 1991, p. 290.
 691. Yu, N. T., J. F. R. Kuck, and C. C. Asskren. Red fluorescence in older and brunescent human lenses. Invest. Ophthalmol. Vis. Sci. 18: 1278–1280, 1979.
 692. Yue, D. K., S. McLennan, L. Delbridge, D. J. Handelsman, T. Reeve, and J. R. Turtle. The thermal stability of collagen in diabetic rats: correlation with severity of diabetes and non‐enzymatic glycosylation. Diabetologia 24: 282–285, 1983.
 693. Zigler, J. S., Jr., and J. D. Goosey. Aging of protein molecules: lens crystallins as a model system. Trends Biochem. Sci. 6: 133–136, 1981.
 694. Zigler, J. S., Jr., and J. D. Goosey. Singlet oxygen as a possible factor in human senile nuclear cataract development. Curr. Eye Res. 3: 59–65, 1984.
 695. Zigler, J. S., Jr., J. B. Sidbury, Jr., B. S. Yamanashi, and M. Wolbarsht. Studies on brunescent cataracts. Ophthalmic Res. 8: 379–387, 1976.
 696. Zigman, S. Coloration of human lenses by near ultraviolet photo‐oxidized tryptophan. Exp. Eye Res. 13: 70–76, 1972.
 697. Zigman, S. Tryptophan excited states in the lens. Doc. Ophthalmol. 8: 267–274, 1976.
 698. Zigman, S., Photochemical mechanisms in cataract formation. In: Mechanisms of Cataract Formation in the Human Lens, edited by G. Duncan. New York: Academic Press, 1981, p. 117–149.
 699. Zigman, S., G. Griess, T. Yulo, and J. Schultz. Ocular protein alterations by near UV light. Exp. Eye Res. 23: 555–567, 1973.
 700. Zigman, S., T. Groff, T. Yulo, and G. Griess. Light extinction and protein in lens. Exp. Eye Res. 23: 555–567, 1976.
 701. Zigman, S., T. Yulo, and G. A. Griess. Inactivation of catalase by near ultraviolet light and tryptophan photoproducts. Mol. Cell. Biochem. 11: 149–154, 1976.
 702. Zika, J. M., and L. Klein. Relative and absolute changes in skin collagen mass in the rat. Biochim. Biophys. Acta 229: 509–515, 1971.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Aging of Long‐Lived Proteins: Extracellular Matrix (Collagens, Elastins, Proteoglycans) and Lens Crystallins
 

How to Cite

David R. Sell, Vincent M. Monnier. Aging of Long‐Lived Proteins: Extracellular Matrix (Collagens, Elastins, Proteoglycans) and Lens Crystallins. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 235-305. First published in print 1995. doi: 10.1002/cphy.cp110110