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Research Highlights

Study of naked mole rats challenges long-held theory of aging

A recent study of long-lived naked mole rats calls into question the conventional theory that aging results from the accumulation of oxidative damage. Naked mole rats can live into their late 20s with steady levels of oxidative damage that begin at a young age. Another biological mechanism—resilient proteins that adapt to oxidative stress—may be the key to their successful aging, according to NIA-funded researchers at the University of Texas Health Science Center in San Antonio.

The research reveals another exception to the widely accepted theory that oxidative damage to proteins and other molecules leads to aging. In naked mole rats, proteins sustain oxidative damage early on yet remain stable throughout the rats’ long lives, the scientists found. In contrast, proteins in short-lived mice show increasing levels of oxidative damage as they get older.

In comprehensive testing and analysis of oxidation states of protein cysteines (sulfur-containing amino acids), the researchers found that, compared with mice, mole rats had higher levels of total cysteine and no age-related changes in cysteine oxidation during more than 20 years. The mole rats also showed unusual resistance to protein unfolding and lower levels of protein degradation during aging.

The results suggest a new biochemical mechanism underlying longevity: the ability of oxidized proteins to maintain their structural stability and integrity.

Reference: Pérez, V.I., et al. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci USA. 2009. 106(9):3059–64.