TY - JOUR
T1 - How stem cells age and why this makes us grow old
AU - Sharpless, Norman E.
AU - DePinho, Ronald A.
N1 - Funding Information:
We thank E. Sahin, J.-H. Paik, T. Letai and K. Mohlke for critical reading and advice on the manuscript. R.A.D. is a director, co-founder and scientific advisor of AVEO Pharmaceuticals, Inc. in Cambridge, Massachusetts, USA, and is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar. This work was supported by grants from the Sidney Kimmel Foundation for Cancer Research (N.E.S.), the Ellison Medical Foundation (N.E.S. and R.A.D.), the American Federation of Aging Research (N.E.S.), the Burroughs Wellcome Fund (N.E.S.) and the US National Institutes of Health (R.A.D.). R.A.D. is supported by the LeBow Fund to Cure Myeloma and the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science.
PY - 2007/9
Y1 - 2007/9
N2 - Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16INK4a, may also induce an unwanted consequence: a decline in the replicative function of certain stem-cell types with advancing age. This decreased regenerative capacity appears to contribute to some aspects of mammalian ageing, with new findings pointing to a 'stem-cell hypothesis' for human age-associated conditions such as frailty, atherosclerosis and type 2 diabetes.
AB - Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16INK4a, may also induce an unwanted consequence: a decline in the replicative function of certain stem-cell types with advancing age. This decreased regenerative capacity appears to contribute to some aspects of mammalian ageing, with new findings pointing to a 'stem-cell hypothesis' for human age-associated conditions such as frailty, atherosclerosis and type 2 diabetes.
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U2 - 10.1038/nrm2241
DO - 10.1038/nrm2241
M3 - Review article
C2 - 17717515
AN - SCOPUS:34548153747
SN - 1471-0072
VL - 8
SP - 703
EP - 713
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
IS - 9
ER -