Epigenetics of Calorie Restriction

An open access review paper in PDF format that discusses some of the fine details of current research into the mechanisms by which calorie restriction slows aging. This work is aimed at establishing a level of understanding sufficient to produce calorie restriction mimetic drugs that also slow aging: "The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors and caloric restriction is by far the most effective and established environmental manipulation for extending the lifespan of various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modifications, are believed to dynamically influence the chromatin structure resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulations in response to caloric restriction and how this impacts cellular senescence, aging and potential extension of a healthy lifespan for humans. Enhanced understanding of the important role of epigenetics in control of aging through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases."

Link: http://www.biomedcentral.com/1741-7015/9/98


The paper is interesting, but does not focus on whether senescence is driven by maintenance- (DNMT1) or by 'de novo-' (DNMT3b) methylation. It is probably oversimplistic to regard a cell as a state machine, but if we do, it would seem that increasing maintenance- (DNMT1) and decreasing de novo-methylation would slow cellular evolution from 'stemness' toward senescence. Quite likely incorrect, but this may be in line with some statements in the paper -
"Chromatin modifications: The driving force of senescence and aging?"

Posted by: Lou Pagnucco at September 4th, 2011 10:43 AM

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