Mutation theory of aging, assessed in transgenic mice and knockout mice

被引：27

作者：

Ono, T ^{[1
]}

Uehara, Y ^{[1
]}

Saito, Y ^{[1
]}

Ikehata, H ^{[1
]}

机构：

[1] Tohoku Univ, Dept Cell Biol, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan

来源：

MECHANISMS OF AGEING AND DEVELOPMENT | 2002年 / 123卷 / 12期

关键词：

mutation; aging; transgenic mouse; knockout mouse;

D O I：

10.1016/S0047-6374(02)00090-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A vital question in the mutation theory of aging is whether mutation accumulates with age. If it does, what are the causes and consequences of the accumulation of mutation? The recent development of transgenic mice has made it possible to study mutation in different kinds of tissues and at a molecular level. An application of these mice to the study of age-dependent alteration has revealed that mutation does accumulate in the aging process. Studies have also revealed several important characteristics of mutation associated with aging. (1) The rate of age-dependent increase of mutant frequency varies among different types of tissue. (2) The rate is not in parallel with the cell proliferation rate of the tissue. (3) Some types of mutation are unique to specific tissues, suggesting the presence of a mechanism of mutation relative to tissue type. On the other hand, several kinds of knockout mice defective in DNA repair have been shown to exhibit tissue lesions and shortened life span. These characteristics provide a new view on the relationship between aging and the genome maintenance system. Here we review the current status of research on the correlation between mutation and aging undertaken by the use of transgenic and knockout mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：1543 / 1552

页数：10

共 53 条

[1] Tissues of MSH2-deficient mice demonstrate hypermutability on exposure to a DNA methylating agent [J].

Andrew, SE ;

McKinnon, M ;

Cheng, BS ;

Francis, A ;

Penney, J ;

Reitmair, AH ;

Mak, TW ;

Jirik, FR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (03) :1126-1130

[2] Tumors of DNA mismatch repair-deficient hosts exhibit dramatic increases in genomic instability [J].

Baross-Francis, A ;

Andrew, SE ;

Penney, JE ;

Jirik, FR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8739-8743

[3] Elevated mutant frequencies and increased C:G→T:A transitions in Mlh1-/- versus Pms2-/- murine small intestinal epithelial cells [J].

Baross-Francis, A ;

Makhani, N ;

Liskay, RM ;

Jirik, FR .

ONCOGENE, 2001, 20 (05) :619-625

[4] MEASUREMENT OF HPRT MUTANT FREQUENCIES IN LYMPHOCYTE-T FROM HEALTHY-HUMAN POPULATIONS [J].

BRANDA, RF ;

SULLIVAN, LM ;

ONEILL, JP ;

FALTA, MT ;

NICKLAS, JA ;

HIRSCH, B ;

VACEK, PM ;

ALBERTINI, RJ .

MUTATION RESEARCH, 1993, 285 (02) :267-279

[5]

Buettner VL, 1999, ENVIRON MOL MUTAGEN, V33, P320, DOI 10.1002/(SICI)1098-2280(1999)33:4<320::AID-EM9>3.0.CO

[6]

2-S

[7] Rapid accumulation of genome rearrangements in liver but not in brain of old mice [J].

Dolle, MET ;

Giese, H ;

Hopkins, CL ;

Martus, HJ ;

Hausdorff, JM ;

Vijg, J .

NATURE GENETICS, 1997, 17 (04) :431-434

[8] Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine [J].

Dollé, MET ;

Snyder, WK ;

Gossen, JA ;

Lohman, PHM ;

Vijg, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (15) :8403-8408

[9] Mutation in the mismatch repair gene Msh6 causes cancer susceptibility [J].

Edelmann, W ;

Yang, K ;

Umar, A ;

Heyer, J ;

Lau, K ;

Fan, KH ;

Liedtke, W ;

Cohen, PE ;

Kane, MF ;

Lipford, JR ;

Yu, NJ ;

Crouse, GF ;

Pollard, JW ;

Kunkel, T ;

Lipkin, M ;

Kolodner, R ;

Kucherlapati, R .

CELL, 1997, 91 (04) :467-477

[10]

FINCH CE, 1990, LONGEVITY SENESCENCE, P428

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