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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 19, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp001
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Kleemeier Award Lecture 2008—The Canary in the Coal Mine: Telomeres and Human Healthspan

Rita B. Effros1,2

1 Department of Pathology and Laboratory Medicine
2 UCLA AIDS Institute, David Geffen School of Medicine at University of California, Los Angeles

Address correspondence to Rita B. Effros, PhD, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1732. Email: reffros{at}mednet.ucla.edu


  Abstract

Telomeres, the repeated series of DNA sequences that cap the ends of linear chromosomes, become shorter during cell division and oxidative stress. Shortened telomeres have been documented in a wide variety of pathologies associated with aging and are also predictive of early mortality in the very old. However, telomere shortening—like the canary in the coal mine—is not the cause of the deleterious effects, but rather, the harbinger of increased health risk. Using immune responses to infection as a model system to further analyze the link between telomeres and age-related disease, we have demonstrated that the end-stage T cell with shortened telomeres is reduced in antiviral immune function and secretes large amounts of so-called proinflammatory factors. Our research has documented that maintaining high levels of the telomere-extending enzyme, telomerase, by either genetic manipulation or exposure of T cells to chemical telomerase activators, not only retards telomere loss but also restores a more youthful functional profile to the T cells. These observations suggest possible novel telomerase-based therapeutic approaches to enhancing healthspan in the elderly population.

Keywords Kleemeier award lecture; Telomeres; Human healthspan; Immune; T cells

Received: January 2, 2009; Accepted: January 2, 2009

Decision Editor: Huber R. Warner, PhD


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