title: Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet.
abstract: Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.
authors.affiliation: Department of Neurology, 1470 Madison Ave., 9-119, New York, NY 10029, USA.
authors.forename: Cesar L
authors.initials: CL
authors.lastname: Moreno
authors.affiliation: Departments of Neuroscience, Endocrinology, and Geriatrics, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave., 9-119, New York, NY 10029, USA. Electronic address: charles.mobbs@mssm.edu.
authors.forename: Charles V
authors.initials: CV
authors.lastname: Mobbs
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D019175:DNA Methylation; D055423:Diet, Ketogenic; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D062385:Hydroxybenzoates; C032948:3-hydroxybenzoic acid; D050882:CREB-Binding Protein; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D006655:Histone Deacetylases
keywords: Aging; Beta-hydroxybutyrylation; Caloric restriction; Cbp; Creb-binding protein; Dietary restriction; HDAC inhibitor; Histone acetylation; Ketogenic diet; Sirtuin