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J Gerontol A Biol Sci Med Sci. 2009 May;64(5):511-5. doi: 10.1093/gerona/glp001. Epub 2009 Feb 19.

Kleemeier Award Lecture 2008--the canary in the coal mine: telomeres and human healthspan.

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  • 1Department 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, USA. reffros@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.

PMID:
19228779
PMCID:
PMC2800806
DOI:
10.1093/gerona/glp001
[PubMed - indexed for MEDLINE]
Free PMC Article
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