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| Item Type: | Article |
|---|---|
| Title: | A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts |
| Creators Name: | Jäger, K. and Mensch, J. and Grimmig, M.E. and Neuner, B. and Gorzelniak, K. and Türkmen, S. and Demuth, I. and Hartmann, A. and Hartmann, C. and Wittig, F. and Sporbert, A. and Hermann, A. and Fuellen, G. and Möller, S. and Walter, M. |
| 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 target of rapamycin suppression. A mechanistic link between telomeres and a tumor suppressor mechanism supports the hypothesis that replicative aging fulfills a tumor suppressor function and motivates previously unknown antitumor and antiaging strategies. |
| Keywords: | Aging, Fibroblasts, Gene Silencing, TOR Serine-Threonine Kinases, Telomere |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 8 |
| Number: | 33 |
| Page Range: | eabk2814 |
| Date: | August 2022 |
| Official Publication: | https://doi.org/10.1126/sciadv.abk2814 |
| PubMed: | View item in PubMed |
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