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Cold Spring Harb Perspect Med. 2015 Sep 18;5(10). pii: a025130. doi: 10.1101/cshperspect.a025130.

DNA Damage, DNA Repair, Aging, and Neurodegeneration.

Author information

1
Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen, Denmark.
2
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
3
Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen, Denmark Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.

Abstract

Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span.

PMID:
26385091
PMCID:
PMC4588127
DOI:
10.1101/cshperspect.a025130
[Indexed for MEDLINE]
Free PMC Article

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