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Author summary of the paper

Posted by jmdelgar on 04 Jan 2013 at 14:05 GMT

Aging can be defined as the accumulation of physiological changes that are progressive, deleterious, universal and thus far irreversible. Aging damage occurs to molecules (DNA, proteins, lipids), cells, and organs. Damage associated with the aging process increases the probability that diseases of old age will occur. A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in major DNA repair mechanisms mostly result in accelerated aging and reduced brain function, so it is assumed that consequence of progressive damage in genome must play a central role in brain aging. We show that elimination of DNA polymerase mu, a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, although reduces moderately DNA repair, surprisingly, improves brain aging decay. Using associative learning and long-term potentiation experiments, we demonstrate that Polmu-/- mice maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polmu-/- mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function.

No competing interests declared.