Abstract
Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H- ras , c- myc , and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c- fos proto-oncogene. The loss of c- fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c- fos ; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.
Keywords
Affiliated Institutions
Related Publications
Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells.
Human diploid fibroblast cells lose replicative potential after a certain number of population doublings. We use this experimental system to investigate the role of oxidative da...
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescenc...
Pulsatile and steady flow induces c‐<i>fos</i> expression in human endothelial cells
Abstract The effects of pulsatile and steady fluid flow on the mRNA levels of proto‐oncogenes c‐ fos , c‐ jun , and c‐ myc in cultured human umbilical vein endothelial cells (HU...
Repression of the basal c-fos promoter by wild-type p53
Mutations in the p53 gene are the most common genetic alterations observed in many inherited and sporadic forms of human cancer. Recent studies indicate that wild-type p53 may b...
Replicative Senescence: the Human Fibroblast Comes of Age
Human diploid fibroblasts undergo replicative senescence predominantly because of arrest at the G 1 /S boundary of the cell cycle. Senescent arrest resembles a process of termin...
Publication Info
- Year
- 1990
- Type
- article
- Volume
- 247
- Issue
- 4939
- Pages
- 205-209
- Citations
- 477
- Access
- Closed
External Links
Social Impact
Social media, news, blog, policy document mentions
Citation Metrics
Cite This
Identifiers
- DOI
- 10.1126/science.2104680