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

doi:10.1016/S0092-8674(00)80580-2

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 journal › Article › peer-review

1072 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 language	English
Pages (from-to)	701-712
Number of pages	12
Journal	Cell
Volume	96
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(00)80580-2
Publication status	Published - 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)

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

Access to Document

10.1016/S0092-8674(00)80580-2

Fingerprint Dive into the research topics of 'Longevity, stress response, and cancer in aging telomerase-deficient mice'. Together they form a unique fingerprint.

Cite this

@article{8787bbd0364f494fbcd0a1fd8656065a,

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

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.",

author = "Rudolph, {Karl Lenhard} and Sandy Chang and Lee, {Han Woong} and Maria Blasco and Gottlieb, {Geoffrey J.} and Carol Greider and DePinho, {Ronald A.}",

note = "Funding Information: We thank Steven Artandi, Lynda Chin, Ronan O{\textquoteright}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). ",

year = "1999",

month = mar,

day = "5",

doi = "10.1016/S0092-8674(00)80580-2",

language = "English",

volume = "96",

pages = "701--712",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0033525558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033525558&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(00)80580-2

DO - 10.1016/S0092-8674(00)80580-2

M3 - Article

C2 - 10089885

AN - SCOPUS:0033525558

VL - 96

SP - 701

EP - 712

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Cite this