TY - JOUR
T1 - Longevity, stress response, and cancer in aging telomerase-deficient mice
AU - Rudolph, Karl Lenhard
AU - Chang, Sandy
AU - Lee, Han Woong
AU - Blasco, Maria
AU - Gottlieb, Geoffrey J.
AU - Greider, Carol
AU - DePinho, Ronald A.
N1 - 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).
PY - 1999/3/5
Y1 - 1999/3/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(00)80580-2
DO - 10.1016/S0092-8674(00)80580-2
M3 - Article
C2 - 10089885
AN - SCOPUS:0033525558
SN - 0092-8674
VL - 96
SP - 701
EP - 712
JO - Cell
JF - Cell
IS - 5
ER -