Somatic mutations in aging, cancer and neurodegeneration

被引:139
作者
Kennedy, Scott R. [1 ]
Loeb, Lawrence A. [1 ,2 ]
Herr, Alan J. [1 ]
机构
[1] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Biochem, Seattle, WA 98195 USA
关键词
Somatic mutation theory of aging; Mitochondria; Ageing; Cancer; Neurodegeneration; MITOCHONDRIAL-DNA DELETIONS; HPRT MUTANT FREQUENCIES; T-LYMPHOCYTES; ALZHEIMERS-DISEASE; MOLECULAR-MECHANISMS; MUTATOR PHENOTYPE; POLYMERASES DELTA; GENOTOXIC STRESS; CELL-DEATH; LIFE-SPAN;
D O I
10.1016/j.mad.2011.10.009
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The somatic mutation theory of aging posits that the accumulation of mutations in the genetic material of somatic cells as a function of time results in a decrease in cellular function. In particular, the accumulation of random mutations may inactivate genes that are important for the functioning of the somatic cells of various organ systems of the adult, result in a decrease in organ function. When the organ function decreases below a critical level, death occurs. A significant amount of research has shown that somatic mutations play an important role in aging and a number of age related pathologies. In this review, we explore evidence for increases in somatic nuclear mutation burden with age and the consequences for aging, cancer, and neurodegeneration. We then review evidence for increases in mitochondrial mutation burden and the consequences for dysfunction in the disease processes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:118 / 126
页数:9
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