Role of MicroRNA Processing in Adipose Tissue in Stress Defense and Longevity

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...

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Bibliographic Details
Published in:Cell metabolism 2012-09, Vol.16 (3), p.336-347
Main Authors: Mori, Marcelo A., Raghavan, Prashant, Thomou, Thomas, Boucher, Jeremie, Robida-Stubbs, Stacey, Macotela, Yazmin, Russell, Steven J., Kirkland, James L., Blackwell, T. Keith, Kahn, C. Ronald
Format: Article
Language:English
Subjects:
Adipose Tissue - metabolism
Aging - metabolism
Animals
Biological Evolution
Caenorhabditis elegans
Cell Culture Techniques
DNA Primers - genetics
Gene Expression Regulation, Enzymologic - physiology
Humans
Longevity - genetics
Longevity - physiology
Mice
Mice, Knockout
MicroRNAs - metabolism
Oxidative Stress - genetics
Ribonuclease III - genetics
Ribonuclease III - metabolism
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Summary: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. ► miRNAs and Dicer decline with age in mouse fat, human preadipocytes, and C. elegans ► In mice and C. elegans, this is prevented by calorie restriction ► In cultured cells, Dicer is downregulated by oxidative and UV stress ► Dicer levels in mouse fat or worm intestine influence stress defense and longevity
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2012.07.017