Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination

Aging Cell

Nuno M. V. Gomes⁴  Oliver A. Ryder¹  Marlys L. Houck¹  Suellen J. Charter¹  William Walker⁴  Nicholas R. Forsyth²  Steven N. Austad⁵  Chris Venditti³  Mark Pagel³  Jerry W. Shay⁴ 

[1] Conservation and Research for Endangered Species, Genetics Division, Arnold and Mabel Beckman Center for Conservation Research, Escondido, CA 92027, USA;Keele University Medical School, Stoke on Trent STA 7QB, UK;School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6BX, UK;Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA;Barshop Center for Longevity and Aging Studies, San Antonio, TX 78245, USA

关键词: evolution of telomeres;    immortalization;    telomerase;    replicative aging;    senescence;   

DOI  :  10.1111/j.1474-9726.2011.00718.x

来源: Wiley

【 摘 要 】

Summary

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 > 60 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny-based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (< 20 kb, 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-evolved with body size. Multiple independent times smaller, shorter-lived species changed to having longer telomeres and expressing telomerase. Trade-offs involving reducing the energetic/cellular costs of specific oxidative protection mechanisms (needed to protect < 20 kb 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-like 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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland