title: Telomerase activity coevolves with body mass not lifespan.
abstract: In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Seluanov
authors.forename: Zhuoxun
authors.initials: Z
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Hine
authors.forename: Tais H C
authors.initials: TH
authors.lastname: Sasahara
authors.forename: Antonio A C M
authors.initials: AA
authors.lastname: Ribeiro
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Catania
authors.forename: Daven C
authors.initials: DC
authors.lastname: Presgraves
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001835:Body Weight / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010802:Phylogeny; D051381:Rats; D011916:Rats, Inbred F344; D012377:Rodentia / Q000502:physiology*; D013045:Species Specificity; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry
chemical_list: D019098:Telomerase