Genetic contribution to aging: deleterious and helpful genes define life expectancy.

Authors: Lao JI; Montoriol C; Morer I; Beyer K

Abstract: For the best understanding of aging, we must consider a genetic pool in which genes with negative effects (deleterious genes that shorten the life span) interact with genes with positive effects (helpful genes that promote longevity) in a constant epistatic relationship that results in a modulation of the final expression under particular environmental influences. Examples of deleterious genes affecting aging (predisposition to early-life pathology and disease) are those that confer risk for developing vascular disease in the heart, brain, or peripheral vessels (APOE, ACE, MTFHR, and mutation at factor II and factor V genes), a gene associated with sporadic late-onset Alzheimer's disease (APOE E4), a polymorphism (COLIA1 Sp1) associated with an increased fracture risk, and several genetic polymorphisms involved in hormonal metabolism that affect adverse reactions to estrogen replacement in postmenopausal women. In summary, the process of aging can be regarded as a multifactorial trait that results from an interaction between stochastic events and sets of epistatic alleles that have pleiotropic age-dependent effects. Lacking those alleles that predispose to disease and having the longevity-enabling genes (those beneficial genetic variants that confer disease resistance) are probably both important to such a remarkable survival advantage.

Keywords: Aged; Aged, 80 and over; Aging/*genetics/physiology; Animals; Apolipoproteins/genetics; Cognition/physiology; Female; Genes, Mitochondrial; HLA Antigens/genetics; Humans; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; *Life Expectancy; Neoplasms/genetics; Osteoporosis/genetics; Risk Factors; Vascular Diseases/genetics
Journal: Annals of the New York Academy of Sciences
Volume: 1057
Pages: 50-63
Date: Jan. 10, 2006
PMID: 16399887
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Categories: Single-Nucleotide Polymorphism
Citation:

Lao JI, Montoriol C, Morer I, Beyer K (2005) Genetic contribution to aging: deleterious and helpful genes define life expectancy. Annals of the New York Academy of Sciences 1057: 50-63.


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