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Pérez VI, Buffenstein R, Masamsetti V, Leonard S, Salmon AB, Mele J, Andziak B, Yang T, Edrey Y, Friguet B, Ward W, Richardson A, Chaudhuri A. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3059-64. PubMed.
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University of Washington
I thank Amber Dance for this nice story on these two important recent publications. I would certainly agree with my friend George Perry that oxidative stress cannot be the SOLE cause of biological aging. Aging is clearly multifactorial. An important role for oxidative damage to macromolecules however, in my opinion, has not been falsified. Note that the abstract of the referenced PNAS paper from our San Antonio brethren on the remarkably long-lived naked mole rats (MRs) emphasizes that, compared to aging lab mice, “…MRs have markedly attenuated age-related accrual of oxidation damage to thiol groups…” That paper makes some intelligent suggestions regarding what might have evolved, in the mole rats, to counter such accumulations of damage and the impact of such damage, but the fact that the damage is hardly accumulating in these long-lived rodents could be interpreted as evidence that such accumulation can contribute to the shorter life spans of lab mice and to aspects of their more problematic health spans.
It is very nice to see that the Landfield group has gone on to develop comprehensive expression array studies of the aging hippocampal CA1 region throughout the adult life span and to correlate the changes in gene expression with a cognitive assay. It will be important to extend these studies to species other than the Fischer 344 rat, to employ the newer transcriptome assays, which will permit quantitation of low copy-number molecules such as transcription factors, and to utilize additional cognitive assays. But their interpretations are very imaginative and do form a basis for some hypothesis testing via the creation of conditional transgenic mice.
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