DNA Damage Theory of Aging - Conclusions


Numerous studies have shown that DNA damage accumulates in brain, muscle, liver, kidney, and in long-lived stem cell. These accumulated DNA damages are the likely cause of the decline in gene expression and loss of functional capacity observed with increasing age. On the other hand, accumulation of mutations, as distinct from DNA damages, is not a plausible candidate as the primary cause of aging. A calorie-restricted diet in mammals improves lifespan, and this improvement is associated with a decrease in oxidative DNA damage. Several inherited genetic defects in ability to repair DNA damage give rise to premature aging suggesting a causal relationship between DNA damage and aging. In comparisons of different mammalian species that differ in lifespan, DNA repair capacity is found to correlate with lifespan. The principal source of the DNA damages leading to normal aging appears to be reactive oxygen species, produced as byproducts of normal cellular metabolism.

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