New research suggests that SIRT1, the protein best known for the longevity-promoting effects of calorie restriction, may also play a crucial role in the aging process.
David A Sinclair and colleagues found that SIRT1 is responsible for packaging DNA into chromatin, and thus controls whether a gene is switched on or off. However, if DNA damage occurs, SIRT1 deserts its gene expression post and helps to repair the damaged DNA. This is where the problem arises. Whilst SIRT1 is busy carrying out repairs to the damaged DNA it cannot control gene expression, leaving gene expression to run out of control. A situtation which eventually leads to changes in gene expression that that parallel those seen in the aging mouse brain. And, the researchers suspect, other body tissue as well.
“The critical protein controls both which genes are off and on as well as DNA repair; it’s used for both processes, and that’s the catch,” said David Sinclair in a news release. “As cells accumulate DNA damage, the protein can’t do both jobs sufficiently.”
However, the good news is that the researchers also found evidence to suggest that it may be possible to slow the aging process. Research showed that mice with extra SIRT1 were more able to repair damaged DNA while also keeping gene expression under control, thus helping them to maintain a youthful gene profile. Therefore, the hope is that the discovery of a drug that stimulates SIRT1 production may at long last provide us with a fountain of youth.
Oberdoerffer P, MIchan S, McVay M, et al. SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging. Cell 2008;135:907-918. doi:10.1016/j.cell.2008.10.025
News release: Where does the gene activity of youth go? New findings may hold the key. Cell Press. November 26th 2008.
