A dual role of p21 in stem cell aging

被引：64

作者：

Ju, Zhenyu ^{[1
]}

Choudhury, Aaheli Roy ^{[1
]}

Rudolph, K. Lenhard ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Gastroenterol Hepatol & Endrocrinol, D-30625 Hannover, Germany

来源：

BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS | 2007年 / 1100卷

关键词：

aging; p21; stem cells; telomeres;

D O I：

10.1196/annals.1395.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A decline in adult stem cell function occurs during aging, likely contributing to the decline in organ homeostasis and regeneration with age. An emerging field in aging research is to analyze molecular pathways limiting adult stem cell function in response to macromolecular damage accumulation during aging. Current data suggest that the p21 cell cycle inhibitor has a dual role in stem cell aging: On one hand, p21 protects adult stem cells from acute genotoxic stress by preventing inappropriate cycling of acutely damaged stem cells. On the other hand, p21 activation impairs stem cell function and survival of aging telomere dysfunctional mice indicating that p21 checkpoint function is disadvantageous in the context of chronic and persistent damage, which accumulates during aging. This article focuses on these dual roles of p21 in aging stem cells.

引用

页码：333 / 344

页数：12

共 67 条

[1] ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage [J].

Aladjem, MI ;

Spike, BT ;

Rodewald, LW ;

Hope, TJ ;

Klemm, M ;

Jaenisch, R ;

Wahl, GM .

CURRENT BIOLOGY, 1998, 8 (03) :145-155

[2] Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts [J].

Alcorta, DA ;

Xiong, Y ;

Phelps, D ;

Hannon, G ;

Beach, D ;

Barrett, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13742-13747

[3] STRUCTURE AND FUNCTION OF TELOMERES [J].

BLACKBURN, EH .

NATURE, 1991, 350 (6319) :569-573

[4] Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].

Blasco, MA ;

Lee, HW ;

Hande, MP ;

Samper, E ;

Lansdorp, PM ;

DePinho, RA ;

Greider, CW .

CELL, 1997, 91 (01) :25-34

[5] Bypass of senescence after disruption of p21(CIP1/WAF1) gene in normal diploid human fibroblasts [J].

Brown, JP ;

Wei, WY ;

Sedivy, JM .

SCIENCE, 1997, 277 (5327) :831-834

[6] RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY [J].

BRUGAROLAS, J ;

CHANDRASEKARAN, C ;

GORDON, JI ;

BEACH, D ;

JACKS, T ;

HANNON, GJ .

NATURE, 1995, 377 (6549) :552-557

[7] Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors [J].

Campisi, J .

CELL, 2005, 120 (04) :513-522

[8] Association between telomere length in blood and mortality in people aged 60 years or older [J].

Cawthon, RM ;

Smith, KR ;

O'Brien, E ;

Sivatchenko, A ;

Kerber, RA .

LANCET, 2003, 361 (9355) :393-395

[9] Stem cell repopulation efficiency but not pool size is governed by p27kip1 [J].

Cheng, T ;

Rodrigues, N ;

Dombkowski, D ;

Stier, S ;

Scadden, DT .

NATURE MEDICINE, 2000, 6 (11) :1235-1240

[10] Hematopoietic stem cell quiescence maintained by p21cip1/waf1 [J].

Cheng, T ;

Rodrigues, N ;

Shen, HM ;

Yang, YG ;

Dombkowski, D ;

Sykes, M ;

Scadden, DT .

SCIENCE, 2000, 287 (5459) :1804-1808

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