A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts.

ABSTRACT: Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD). The function of this silencing mechanism is unknown. We determined a set of 2322 genes with high positional conservation across replicatively aging species that includes known and candidate TPE-OLD genes that may mitigate potentially harmful effects of replicative aging. Notably, we identified PPP2R2C as a tumor suppressor gene, whose up-regulation by TPE-OLD in aged human fibroblasts leads to dephosphorylation of p70S6 kinase and mammalian targe

SUBMITTER: Jager K 

PROVIDER: S-EPMC9385144 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature