Development

Old Stem Cells Rejuvenated

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Science  22 Feb 2013:
Vol. 339, Issue 6122, pp. 884-885
DOI: 10.1126/science.339.6122.884-d

Hematopoietic stem cells (HSCs) in the bone marrow give rise to all cells of the blood, but with age, this capacity decreases. Sirtuin 3 (SIRT3) is a deactylase expressed in mitochondria that can control the production of damaging reactive oxygen species (ROS) by, for example, improving the antioxidative activity of other enzymes. Brown et al. observed that SIRT3 is highly expressed in the HSCs of young mice but not in older mice. In mice genetically engineered to lack SIRT3, the number of HSCs declined in older animals and, consequently, reduced the number of differentiated blood cells. In contrast, young mice lacking SIRT3 showed no such effects. In bone marrow transplant assays, only HSCs from young wild-type mice or young SIRT3-deficient mice could reconstitute blood in recipient mice. SIRT3-deficient HSCs from old mice also were susceptible to oxidative stress in vitro and showed reduced survival in vivo. The overexpression of SIRT3 in older SIRT3-deficient HSCs reduced ROS production and boosted the production of blood cells in bone marrow transplantation assays. Thus, the reduced expression of SIRT3 with age probably disrupts mitochondrial homeostasis and increases oxidative stress, thereby compromising stem cell renewal and function. Age-related stem cell degeneration may be reversed by manipulating mitochondrial homeostasis.

Cell Rep. 10.1016/j.celrep.2013.01.005 (2013).

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