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Cell Culture as a Model

Vincent J. Cristofalo, Robert J. Pignolo

10.1002/cphy.cp110104

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 Historical Development of Cell Cultures for the Study of Aging
2 Relevance of in Vitro Cellular Senescence to in Vivo Aging
2.1 Cell Cultures as Models
2.2 Cellular Mortality, Cellular Clocks, and Death as an End Point for Aging
2.3 Aging and Evolution
2.4 In Vivo–In Vitro Parallel Changes
3 Caveats in the Use of Cell Cultures as Models
4 Cellular and Molecular Markers of Senescence in Vitro and in Vivo
5 Mechanistic Studies of in Vitro Replicative Senescence
5.1 Stochastic Mechanisms
5.2 Signal Transduction Pathways
5.3 Genetic Mechanisms
6 Summary and Conclusions
Figure 1. Figure 1.

Heterogeneity of senescent cells in culture. Multiple parallel pathways leading to DNA synthesis, one or more of which may be blocked in senescent cells (*ART*). These block(s) may be overcome in conditionally arrested cells by a variety of manipulations at putative target sites but not in irreversibly arrested cells, except by SV40 infection. PMA, phorbol 12‐myristate 13‐acetate; HC, hydrocortisone.
Figure 2. Figure 2.

Stages in the in vitro life history of normal human diploid fibroblasts. Phase I, outgrowth from explant; phase II, period of vigorous proliferation; phase III, decline in proliferative capacity; phase IV, cessation of proliferation and cell death; phase V, emergence of a stable, viable, but essentially nonproliferating cell population. Dotted line indicates the possibility, as a rare event, phase II cells may transform into an immortalized population acquiring an indefinite proliferation potential.
Figure 3. Figure 3.

Representation of growth states available to young and senescent fibroblasts and the molecular markers that define each state. Gs, senescence‐specific growth state; τ, putative transitional pathways by which conditionally arrested cells may re‐enter cell cycle;?, pathways by which young cells become senescent by an unknown mechanism(s).


Figure 1.

Heterogeneity of senescent cells in culture. Multiple parallel pathways leading to DNA synthesis, one or more of which may be blocked in senescent cells (*ART*). These block(s) may be overcome in conditionally arrested cells by a variety of manipulations at putative target sites but not in irreversibly arrested cells, except by SV40 infection. PMA, phorbol 12‐myristate 13‐acetate; HC, hydrocortisone.



Figure 2.

Stages in the in vitro life history of normal human diploid fibroblasts. Phase I, outgrowth from explant; phase II, period of vigorous proliferation; phase III, decline in proliferative capacity; phase IV, cessation of proliferation and cell death; phase V, emergence of a stable, viable, but essentially nonproliferating cell population. Dotted line indicates the possibility, as a rare event, phase II cells may transform into an immortalized population acquiring an indefinite proliferation potential.



Figure 3.

Representation of growth states available to young and senescent fibroblasts and the molecular markers that define each state. Gs, senescence‐specific growth state; τ, putative transitional pathways by which conditionally arrested cells may re‐enter cell cycle;?, pathways by which young cells become senescent by an unknown mechanism(s).

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Article Title: Cell Culture as a Model
 

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Vincent J. Cristofalo, Robert J. Pignolo. Cell Culture as a Model. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 53-82. First published in print 1995. doi: 10.1002/cphy.cp110104