Most normal human cells have a finite life span. After a limited number of cell divisions, they reach a quiescent state termed senescence. During this process, cell cycle progression is blocked by the activation of p53 and the induction of p16(INK4a). The onset of senescence is controlled by the shortening of telomeres that occurs each time normal human cells divide. The observation that telomeres shortening occurs in vivo suggests that senescence may play a role in the aging process. The enzyme telomerase can extend the life span of human cells by synthesizing new telomeric DNA. This enzyme, absent from most somatic tissues, contains an RNA (hTR) that serves as a template for the synthesis of telomeric DNA and a reverse transcriptase (hTERT) that provides catalytic activity. The forced expression of exogenous hTERT in normal human cells is sufficient to reconstitute telomerase activity, maintain the size of telomere and prevent the induction of senescence. During carcinogenesis, senescence is frequently inhibited by the ectopic expression of telomerase. Although senescence might be detrimental as a potential cause of aging, its evolutionary advantage is to provide an additional obstacle to the development of cancers.
|Translated title of the contribution||Telomere-controlled senescence|
|Number of pages||8|
|State||Published - Apr 1 2000|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)