title: Role of microRNA processing in adipose tissue in stress defense and longevity.
abstract: Excess adipose tissue is associated with metabolic disease and reduced life span, whereas caloric restriction decreases these risks. Here we show that as mice age, there is downregulation of Dicer and miRNA processing in adipose tissue resulting in decreases of multiple miRNAs. A similar decline of Dicer with age is observed in C. elegans. This is prevented in both species by caloric restriction. Decreased Dicer expression also occurs in preadipocytes from elderly humans and can be produced in cells by exposure to oxidative stress or UV radiation. Knockdown of Dicer in cells results in premature senescence, and fat-specific Dicer knockout renders mice hypersensitive to oxidative stress. Finally, Dicer loss-of-function mutations in worms reduce life span and stress tolerance, while intestinal overexpression of Dicer confers stress resistance. Thus, regulation of miRNA processing in adipose-related tissues plays an important role in longevity and the ability of an organism to respond to environmental stress and age-related disease.
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Mori
authors.forename: Prashant
authors.initials: P
authors.lastname: Raghavan
authors.forename: Thomas
authors.initials: T
authors.lastname: Thomou
authors.forename: Jeremie
authors.initials: J
authors.lastname: Boucher
authors.forename: Stacey
authors.initials: S
authors.lastname: Robida-Stubbs
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Macotela
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Russell
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans; D018929:Cell Culture Techniques; D017931:DNA Primers / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; D043244:Ribonuclease III