Comparative biology of mammalian telomeres

Hypotheses on ancestral states and the roles of telomeres in longevity determination

Nuno M V Gomes, Oliver A. Ryder, Marlys L. Houck, Suellen J. Charter, William Walker, Nicholas R. Forsyth, Steven N. Austad, Chris Venditti, Mark Pagel, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

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 (<20kb, 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 <20kb 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.

Original languageEnglish (US)
Pages (from-to)761-768
Number of pages8
JournalAging Cell
Volume10
Issue number5
DOIs
StatePublished - Oct 2011

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Telomere
Telomerase
Mammals
Telomere Shortening
Phenotype
Body Size
Phylogeny
Cell Division
Cultured Cells
Neoplasms

Keywords

  • Evolution of telomeres
  • Immortalization
  • Replicative aging
  • Senescence
  • Telomerase

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Comparative biology of mammalian telomeres : Hypotheses on ancestral states and the roles of telomeres in longevity determination. / Gomes, Nuno M V; Ryder, Oliver A.; Houck, Marlys L.; Charter, Suellen J.; Walker, William; Forsyth, Nicholas R.; Austad, Steven N.; Venditti, Chris; Pagel, Mark; Shay, Jerry W.; Wright, Woodring E.

In: Aging Cell, Vol. 10, No. 5, 10.2011, p. 761-768.

Research output: Contribution to journalArticle

Gomes, NMV, Ryder, OA, Houck, ML, Charter, SJ, Walker, W, Forsyth, NR, Austad, SN, Venditti, C, Pagel, M, Shay, JW & Wright, WE 2011, 'Comparative biology of mammalian telomeres: Hypotheses on ancestral states and the roles of telomeres in longevity determination', Aging Cell, vol. 10, no. 5, pp. 761-768. https://doi.org/10.1111/j.1474-9726.2011.00718.x
Gomes, Nuno M V ; Ryder, Oliver A. ; Houck, Marlys L. ; Charter, Suellen J. ; Walker, William ; Forsyth, Nicholas R. ; Austad, Steven N. ; Venditti, Chris ; Pagel, Mark ; Shay, Jerry W. ; Wright, Woodring E. / Comparative biology of mammalian telomeres : Hypotheses on ancestral states and the roles of telomeres in longevity determination. In: Aging Cell. 2011 ; Vol. 10, No. 5. pp. 761-768.
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