We know that calorie restriction slows the accumulation of nuclear DNA damage - possibly by enhancing DNA repair mechanisms - just as it slows more or less every other age-related change of interest that scientists have investigated. The degree to which ongoing random damage to nuclear DNA contributes to degenerative aging is debated, however:
A paper by Aubrey de Grey outlines his view of nuclear DNA damage and aging: "Since Szilard's seminal 1959 article, the role of accumulating nuclear DNA (nDNA) damage - whether as mutations, i.e. changes to sequence, or as epimutations, i.e. adventitious but persistent alterations to methylation and other decorations of nDNA and histones - has been widely touted as likely to contribute substantially to the aging process throughout the animal kingdom. Such damage certainly accumulates with age and is central to one of the most prevalent age-related causes of death in mammals, namely cancer. However, its role in contributing to the rates of other aspects of aging is less clear. Here I argue that, in animals prone to cancer, evolutionary pressure to postpone cancer will drive the fidelity of nDNA maintenance and repair to a level greatly exceeding that needed to prevent nDNA damage from reaching levels during a normal lifetime that are pathogenic other than via cancer or, possibly, apoptosis resistance." In other words, beyond sufficient work to prevent cancer, we don't need to repair nuclear DNA over a human lifetime. Maybe. This debate is ongoing; there are many others who argue that DNA damage is an important root cause of aging.
A paper caught my eye today - a comparison in mice of the effects of calorie restriction versus Ames dwarfism on nuclear DNA damage. Both extend life, and both reduce DNA damage:
Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis [i.e. Ames dwarfism] significantly increase life span in the mouse and reduce multiple symptoms of aging, including cancer.
To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into Escherichia coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf.
While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57BL/6J background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7- and 15-month-old mice of all four cohorts.
A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR.
Or it may be any of the many other line items of age-related degeneration resisted by both CR and Ames dwarfism. The present trouble with debates on the contribution of nuclear DNA damage to aging is the lack of any good demonstration of extended life (or no extension to life) through prevention of mutational damage only. There are too many confounding factors.