Longevity, stress response, and cancer in aging telomerase-deficient mice

Karl Lenhard Rudolph, Sandy Chang, Han Woong Lee, Maria Blasco, Geoffrey J. Gottlieb, Carol Greider, Ronald A. DePinho

Research output: Contribution to journalArticlepeer-review

1077 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)701-712
Number of pages12
JournalCell
Volume96
Issue number5
DOIs
Publication statusPublished - 1999 Mar 5

Bibliographical note

Funding 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)

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