Abstract
Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.
| Original language | English |
|---|---|
| Pages (from-to) | 319-327 |
| Number of pages | 9 |
| Journal | Cell Reports |
| Volume | 3 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2013 |
Funding
We thank F. Alt and H. Cheng for reagents. This work was supported by Searle Scholars Program (to D.C.), the Hellman Family Faculty Funds (to D.C.), the Ellison Medical Foundation (to D.C.), the NIH (R01AG040990; to D.C.), UCOP TRDRP (to D.C.), American Heart Association (to D.C.), the Siebel Stem Cell Institute (to D.C., X.Q., and M.M.), the CIRM (to X.Q.), and the NSF (to J.S.).
| Funders | Funder number |
|---|---|
| U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China | |
| National Institutes of Health (NIH) | |
| National Institute on Aging | R01AG040990 |
| National Institute on Aging | |
| Ellison Medical Foundation | |
| California Institute for Regenerative Medicine | |
| American the American Heart Association | |
| Harvard Stem Cell Institute | |
| Searle Scholars Program | |
| University of California Office of the President |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology