Expression of p21 is not required for senescence of human fibroblasts.

Senescence and immortalization have been studied in skin fibroblasts derived from two individuals with the Li-Fraumeni syndrome. These cells inherit one wild-type and one mutant p53 allele and lose the former during culture. Despite this loss, cultures of Li-Fraumeni syndrome cells progressed normally from early passage to replicative senescence. Senescent cells also expressed barely detectable levels of p21 mRNA, and, in marked contrast to normal cultured cells, levels of p21 expression decreased during in vitro aging. Further maintenance for up to 10 months of post-mitotic cultures has led to the isolation of cells with an extended lifespan. Four potentially immortal cultures have continued to proliferate, and two have completed more than 110 population doublings. These results indicate that p53 and p21 are not required for replicative senescence in human fibroblasts. However, their inactivation may enhance the probability of spontaneous immortalization.