The Durk Pearson & Sandy Shaw^®
Life Extension News^TM
Volume 12 No. 1 • Feb. 2009

As reported in a recent issue of Cell,¹ scientists have now discovered a new mechanism by which DNA damage accelerates aging. The researchers found that, like Sir2 in yeast, which has been shown to regulate gene activity (whether genes are turned on or off) and to repair DNA breaks in yeast cells, the mammalian version SIRT1 does the same in mouse cells. Moreover, the new study reports, when DNA damage occurs, the Sir complex relocalizes to the site of the damage to promote repair (so as to prevent genomic instability), but in doing so it abandons its prior location, allowing transcriptional changes to take place there that are characteristic of aging. When mice were administered extra copies of the SIRT1 gene, or fed with the sirtuin activator resveratrol, they had more efficient DNA repair without deterioration in the control by SIRT1 of gene expression; moreover, their mean lifespan was extended by 24% to 46%.

Reference

1. Oberdoerffer et al. SIRT1 redistribution on chromatin promotes genetic stability but alters gene expression during aging. Cell 135:907-918 (2008).