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The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of\n                    <jats:italic>tuberous sclerosis complex 1<\/jats:italic>\n                    (\n                    <jats:italic>Tsc1<\/jats:italic>\n                    ) makes the RPCs arrive at the division limit precociously and produce M\u00fcller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of\n                    <jats:italic>Tsc1<\/jats:italic>\n                    -deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of\n                    <jats:italic>hypoxia-induced factor 1-alpha<\/jats:italic>\n                    (\n                    <jats:italic>Hif1a<\/jats:italic>\n                    ), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.\n                  <\/jats:p>","DOI":"10.7554\/elife.70079","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T08:00:55Z","timestamp":1634889655000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.70079","source":"Crossref","is-referenced-by-count":11,"title":["mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent M\u00fcller glia"],"prefix":"10.7554","volume":"10","author":[{"given":"Soyeon","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Joung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sooyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9204-1755","authenticated-orcid":true,"given":"Ji-heon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Hoon","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University","place":["Yonsei, Republic of Korea"]},{"name":"Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhiko","family":"Nishimori","sequence":"additional","affiliation":[{"name":"Department of Obesity and Internal Inflammation; 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