{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:04:13Z","timestamp":1774771453841,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase. Wild species that do\/do not use replicative aging have been reported, but the evolution of different phenotypes and a conceptual framework for understanding their uses of telomeres is lacking. We examined telomeres\/telomerase in cultured cells from &gt;\u200360 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny\u2010based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (&lt;\u200320\u2003kb, as we now see in humans) and repressed telomerase. We argue that the repressed telomerase was a response to a higher mutation load brought on by the evolution of homeothermy. With telomerase repressed, we then see the evolution of replicative aging. Telomere length inversely correlated with lifespan, while telomerase expression co\u2010evolved with body size. Multiple independent times smaller, shorter\u2010lived species changed to having longer telomeres and expressing telomerase. Trade\u2010offs involving reducing the energetic\/cellular costs of specific oxidative protection mechanisms (needed to protect &lt;\u200320\u2003kb telomeres in the absence of telomerase) could explain this abandonment of replicative aging. These observations provide a conceptual framework for understanding different uses of telomeres in mammals, support a role for human\u2010like telomeres in allowing longer lifespans to evolve, demonstrate the need to include telomere length in the analysis of comparative studies of oxidative protection in the biology of aging, and identify which mammals can be used as appropriate model organisms for the study of the role of telomeres in human cancer and aging.<\/jats:p>","DOI":"10.1111\/j.1474-9726.2011.00718.x","type":"journal-article","created":{"date-parts":[[2011,4,25]],"date-time":"2011-04-25T05:23:53Z","timestamp":1303709033000},"page":"761-768","source":"Crossref","is-referenced-by-count":395,"title":["Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination"],"prefix":"10.1111","volume":"10","author":[{"given":"Nuno M. 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