Kleemeier Award Lecture 2008-025EFThe Canary in the Coal Mine: Telomeres and Human Healthspan

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-025EFlike the canary in the coal mine-025EFis 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.