title: Kleemeier Award Lecture 2008--the canary in the coal mine: telomeres and human healthspan.
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.
authors.affiliation: 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, USA. reffros@mednet.ucla.edu
authors.forename: Rita B
authors.initials: RB
authors.lastname: Effros
mesh_terms: D000375:Aging / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000502:physiology*; D016615:Telomere