Abstract
Hypothalamic Sirt1 in aging
Highlights
There is an old Japanese proverb saying, “After rain falls, the ground hardens.” This proverb illustrates what has happened to the research field on the importance of sirtuins in the regulation of aging and longevity
Because our previous study showed that brain-specific Sirt1-overexpressing (BRASTO) transgenic mice significantly enhance physiological responses to dietary restriction (DR), we hypothesized that BRASTO mice could live longer than control wild-type mice under a regular chow-fed condition
Aged BRASTO skeletal muscle was found to maintain youthful morphology and mitochondrial function during the process of aging. This intriguing phenotype was due to the enhancement of the sympathetic nervous tone followed by enhanced neural activity in the DMH and LH during the dark time in aged BRASTO mice; the mechanism by which the signal from the hypothalamus is directed to skeletal muscle remains unknown
Summary
There is an old Japanese proverb saying, “After rain falls, the ground hardens.” This proverb illustrates what has happened to the research field on the importance of sirtuins in the regulation of aging and longevity. Mice overexpressing Sirt1, the mammalian ortholog of Sir2, in the whole body failed to show life span extension (Herrenz et al Nat. Commun., 2010, 1:3). We have demonstrated that increasing Sirt1 in the brain, in the dorsomedial and lateral hypothalamic nuclei (DMH and LH, respectively), delays aging and extends life span (Satoh et al Cell Metab., 2013, 18:416).
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