Sirtuin 3- and Diet-Mediated Regulation of Mitochondrial Function During Aging

Aging is a multifactorial process that results in the gradual damage of a number of cellular systems. Specifically, the decline of mitochondrial function due to hyperacetylation has been implicated in numerous metabolic defects, including senescence. The NAD+-dependent mitochondrial deacetylase, sirtuin 3 (SIRT3) has a marked impact on mitochondrial acetylation status and may be responsible for attenuating oxidative stress. Furthermore, caloric restriction, which induces SIRT3 expression, has been linked to increased longevity. However, the impact of acetylation on mitochondrial function over the lifespan of an organism remains largely unknown. Here, we used a multi-tissue approach to establish the role of SIRT3 and acetylation status in governing aging phenotypes by comparing mitochondrial function and structure in aging mice. C57BL/6 mice in the SIRT3+/+ and −/− condition were fed a control or calorically-restricted diet, and sampled at 5, 15, and 25 months of age. Gastrocnemius, brain, liver and heart ...