Scientists have found a mechanism involving the protein SIRT1 that links DNA damage with age-related changes in gene expression. The study in mice has striking parallels with findings from studies of a similar mechanism in yeast.
Past research has shown that in yeast, the protein Sir2—known for its part in extending life—plays an important role in stabilizing gene function. When DNA damage occurs, Sir2 abandons this role to assist with DNA repair. Without Sir2’s control, genes become unstable and render the yeast sterile, a characteristic associated with aging.
NIH-funded investigators led by Dr. David A. Sinclair of Harvard Medical School in Boston looked at a parallel process in mouse stem cells. They found that SIRT1, the mammalian equivalent of Sir2, helps control gene activity—except when DNA is damaged. In that case, it leaves its normal role to help repair DNA. The resulting changes in gene activity in stem cells are similar to those seen in the brains of aging mice.
Researchers also found longer survival and a lower incidence of tumors in mice with overexpressed SIRT1 than in mice with normal SIRT1 levels. These results indicate that increasing SIRT1 activity or quantity can increase genomic stability and is associated with longer life.