Sirtuin 1, stem cells, aging, and stem cell aging.
OBJECTIVE
New discoveries focused on mitochondrial metabolism and gene silencing and their regulation by the sirtuin family of protein deacetylases is stimulating new ideas on how to improve geriatric medicine. Information about sertuins in stem cell biology is scarce. We consider recent information on sirtuin 1, its role in aging and metabolism in several species and tissues, and attempt to anticipate how it might influence stem cell aging.


RESULTS
Calorie restriction lengthens lifespan, in part, due to mitochondrial metabolism reorganization through sirtuin 1/peroxisome proliferator-activated receptor gamma-coactivator-1alpha-regulated mitochondrial biogenesis. This reduces radical oxygen species levels that cause macromolecule damage, a major contributor to aging. Little is known about these processes in stem cells, whose longevity is implicated in human aging. Recent work indicates that sirtuin 1 influences growth-factor responses and maintenance of stem cells. Sirtuin 1 is required for calorie restriction-induced lifespan extension in mice, and calorie restriction upregulates sirtuin 1 in humans. Sirtuin 1 also appears to influence lineage/cell-fate decisions of stem cells via redox status.


CONCLUSIONS
The same thermodynamic and biochemical mechanisms linked to aging in somatic cells may also work in stem cells. Developments in mitochondrial biology and new drug development based on this knowledge are finding their way into the clinic (i.e. diabetes) and may illuminate new ways of manipulating and using stem cells in medicine.
Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202-5181, USA.
Charlie
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Mantel
Hal E
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Broxmeyer
D000375:Aging; D016922:Cellular Senescence; D006801:Humans; D008136:Longevity; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins