Cell Culture as a Model

Abstract

The sections in this article are: Historical Development of Cell Cultures for the Study of Aging Relevance of in Vitro Cellular Senescence to in Vivo Aging Cell Cultures as Models Cellular Mortality, Cellular Clocks, and Death as an End Point for Aging Aging and Evolution In Vivo–In Vitro Parallel Changes Caveats in the Use of Cell Cultures as Models Cellular and Molecular Markers of Senescence in Vitro and in Vivo Mechanistic Studies of in Vitro Replicative Senescence Stochastic Mechanisms Signal Transduction Pathways Genetic Mechanisms Summary and Conclusions

Intracellular protein synthesis, modifications and aging

“…During cellular aging several putative inhibitors of DNA synthesis have been identified in senescent cells [26,27]. The activity of several of these inhibitors is regulated by phosphorylation.…”

“…The activity of several of these inhibitors is regulated by phosphorylation. For example, a decrease in phosphorylated cyclin E and Cdk2, and failure to phosphorylate the RBI gene product, pllOHh, and the cdc2 product, P34""2 , during cellular aging have been reported [26,27]. It will be important to find out if there are age-related alterations in the phosphorylation state of other cell-cycle-related gene products including proteins involved in synthesis of DNA and RNA, and various transcription factors.…”

Ten Years Later: What Have We Learned About Human Aging from Studie of Cell Cultures?

“…These changes include, but are not limited to, the overexpression of collagenase and stromelysin and a decrease in accumulation of a tissue inhibitor of metalloproteinases (TIMP-1). These and other alterations that occur with cellular aging in vitro and in vivo are reviewed elsewhere (Cristofalo & Pignolo, 1995).…”

“…Some recent evidence suggests that some steps in the cascade of phosphorylations of proteins in this pathway may not operate properly in senescent cells. Many more studies still need to be done to identify these steps and the chemical changes which occur (reviewed in Cristofalo & Pignolo, 1995).…”

Effects of donor age on the expression of a marker of replicative senescence (EPC-1) in human dermal fibroblasts

“…It has also been observed that human fibroblasts that have exhausted their replicative capacity in vitro and cells derived from old donors exhibit some similar characteristics. For example, both late passage cells and cells from old donors exhibit altered cellular morphology, increased size, diminished mitogenic response to serum, growth factors, and calcium ions, decreased saturation density, colony size distribution, and migratory capacity as well as a higher incidence of chromosomal aberrations (reviewed in Cristofalo and Pignolo, 1995). Furthermore, the cells from patients with certain premature aging diseases, such as Werner's syndrome, exhibit a decreased proliferative capacity (Martin, 1978;Goldstein, 1979;Faragher et al, 1993).…”