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Review
. 2008 Jul;15(4):326-31.
doi: 10.1097/MOH.0b013e3283043819.

Sirtuin 1, stem cells, aging, and stem cell aging

Charlie Mantel  1 , Hal E Broxmeyer
Affiliations
Review

Sirtuin 1, stem cells, aging, and stem cell aging

Charlie Mantel et al. Curr Opin Hematol. 2008 Jul.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

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References

    1. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13:2570–2580. - PMC - PubMed
    1. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800. - PubMed
    1. Chen D, Steele AD, Lindquist S, Guarente L. Increase in activity during calorie restriction requires SirT1. Science. 2005;310:1641. - PubMed

    1. Bordone L, Cohen D, Robinson A, et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 2007;6:759–767. This study demonstrates that "knocking in" SIRT1 has the opposite effect on mouse metabolism than SIRT1 gene-deletion, which resembles the caloric restriction phenotype.

    1. Guarente L. Mitochondria--a nexus for aging, calorie restriction, and sirtuins? Cell. 2008;132:171–176. This is a short review of recent studies pointing to the seminal role of mitochondrial metabolism as the main driving force behind dietary influence on lifespan and how SirT1 is an essential integrator of these forces by regulating mitochondrial biogenesis and energy metabolism.

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