Accumulated DNA damage appears to be a limiting factor in the determination of maximum life span. The theory that DNA damage is the primary cause of aging, and thus a principal determinant of maximum life span, has attracted increased interest in recent years. This is based, in part, on evidence in human and mouse that inherited deficiencies in DNA repair genes often cause accelerated aging. There is also substantial evidence that DNA damage accumulates with age in mammalian tissues, such as those of the brain, muscle, liver, and kidney (reviewed by Bernstein et al. and see DNA damage theory of aging and DNA damage (naturally occurring)). One expectation of the theory (that DNA damage is the primary cause of aging) is that among species with differing maximum life spans, the capacity to repair DNA damage should correlate with lifespan. The first experimental test of this idea was by Hart and Setlow who measured the capacity of cells from seven different mammalian species to carry out DNA repair. They found that nucleotide excision repair capability increased systematically with species longevity. This correlation was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. The association between nucleotide excision repair capability and longevity is strengthened by the evidence that defects in nucleotide excision repair proteins in humans and rodents cause features of premature aging, as reviewed by Diderich.
