Universal Aging Mechanism?
As an organism changes, its pattern of gene activation/deactivation and repair changes from a vibrant youthful pattern to a less efficient and effective senescent pattern. Harvard scientists are learning more about some of the underlying mechanisms behind this "genetic control shift of aging."
The researchers found in studies of mammalian stem cells that the protein SIRT1 controls the packaging of DNA into chromatin, thereby setting the youthful pattern of gene activity by keeping select genes switched off. In response to DNA damage, those SIRT1 proteins leave their posts to go off and assist in the necessary repairs. That change in SIRT1's job description leads to shifts in gene activity that parallel those seen in the aging mouse brain, they show. They suspect similar changes would also be found in other body tissues as well.Permanent gene therapy to boost SIRT1 for both gene repair and maintaining a youthful gene activity pattern seems preferable to a daily pill or injection. In fact, genetic therapy will likely replace most pharmaceuticals as we learn more about the underlying physiology and pathology of our organisms. SIRT1 will be but a small part of the overall story of aging. But for now, it appears to be an important early step in our understanding.
" 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 of Harvard Medical School. "As cells accumulate DNA damage, the protein can't do both jobs sufficiently." Once SIRT1 loses control, gene activity goes haywire, a state of affairs that leads to symptoms associated with aging.
Sinclair's team also found what they consider to be good evidence that the aging process can be slowed. Mice with an excess of SIRT1 had an improved ability to repair DNA and prevent those unwanted changes in gene expression. The hope is that those improvements could be reproduced with a drug that stimulates SIRT1, they said. _Eurekalert