title: From cells to organisms: can we learn about aging from cells in culture?
abstract: Can studying cultured cells inform us about the biology of aging? The idea that this may be was stimulated by the first formal description of replicative senescence. Replicative senescence limits the proliferation of normal human cells in culture, causing them to irreversibly arrest growth and adopt striking changes in cell function. We now know that telomere shortening, which occurs in most somatic cells as a consequence of DNA replication, drives replicative senescence in human cells. However, rodent cells also undergo replicative senescence, despite very long telomeres, and DNA damage, the action of certain oncogenes and changes in chromatin induce a phenotype similar to that of replicatively senescent cells. Thus, replicative senescence is an example of the more general process of cellular senescence, indicating that the telomere hypothesis of aging is a misnomer, Cellular senescence appears to be a response to potentially oncogenic insults, including oxidative stress. The growth arrest almost certainly suppresses tumorigenesis, at least in young organisms, whereas the functional changes may contribute to aging, although this has yet to be critically tested. Thus, cellular senescence may be an example of antagonistic pleiotropy. Cross-species comparisons suggest there is a relationship between the senescence of cells in culture and organismal life span, but the relationship is neither quantitative nor direct.
authors: Life Sciences Division, Lawrence Berkeley National Laboratory, Mailstop 84-171, 1 Cyclotron Road, Berkeley, CA 94720, USA. jcampisi@lbl.gov
authors: J
authors: J
authors: Campisi
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D018929:Cell Culture Techniques; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008136:Longevity; D013045:Species Specificity; D019098:Telomerase; D016615:Telomere
chemical_list: D019098:Telomerase