Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR(-/-) mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism.
Bibliographical noteFunding Information:
We thank Steven Artandi, Lynda Chin, Ronan O’Hagan, and Nicole Schreiber-Agus for critical reading of the manuscript, and B. Furman, K. E. Cedeno-Baier, L. Husted, and S. Rao for excellent technical assistance. The work was supported by grants from the National Institutes of Health and American Heart Association grant-in-aid to R. A. D.; R. A. D. is an American Cancer Society Research Professor. Support from the Dana Farber Cancer Institute Cancer Core grant to R. A. D. is acknowledged. K. L. R. is supported by the Deutsche Forschungsgemeinschaft (Ru 745/1-1), and C. G. is supported by the National Institutes of Health. M. B. is supported by the Ministry of Education and Culture of Spain and by the Department of Immunology and Oncology (CSIC-Pharmacia and Upjohn).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)