Role of microRNA processing in adipose tissue in stress defense and longevity

Marcelo A. Mori, Prashant Raghavan, Thomas Thomou, Jeremie Boucher, Stacey Robida-Stubbs, Yazmin MacOtela, Steven J. Russell, James L. Kirkland, T. Keith Blackwell, C. Ronald Kahn

Research output: Contribution to journalArticle

132 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)336-347
Number of pages12
JournalCell Metabolism
Volume16
Issue number3
DOIs
StatePublished - Sep 5 2012

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Mori, M. A., Raghavan, P., Thomou, T., Boucher, J., Robida-Stubbs, S., MacOtela, Y., Russell, S. J., Kirkland, J. L., Blackwell, T. K., & Kahn, C. R. (2012). Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metabolism, 16(3), 336-347. https://doi.org/10.1016/j.cmet.2012.07.017