@article{6ab3ac7f17c747308326d00fdb301afe,
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.",
author = "Mori, {Marcelo A.} and Prashant Raghavan and Thomas Thomou and Jeremie Boucher and Stacey Robida-Stubbs and Yazmin MacOtela and Russell, {Steven J.} and Kirkland, {James L.} and Blackwell, {T. Keith} and Kahn, {C. Ronald}",
note = "Funding Information: We thank J. LaVecchio, G. Buruzula, J. Schroeder, M. Rourk, G. Smyth, S. Rath, and N. Moroz for help with experiments. We also thank M. Merkenschlager and H.M. Kronenberg for providing us with the Dicer lox/lox mice, E. Rosen for providing us with the Adiponectin-Cre mice, E. Cram and I. Kovacevic for providing us with plasmids, B.L. Bass, F. Slack, H. Zhang, S. Kennedy, and the Caenorhabditis Genetics Center for providing us with C. elegans strains, and N. Giorgadze for help in culturing human preadipocytes. M.A.M., Y.M., J.B., S.J.R., and C.R.K. were supported by grants from the NIH (DK082659, DK033201, and AG032869) and grants from the Ellison Foundation, the Joslin Diabetes and Endocrinology Research Center cores (DK036836), and the Mary K. Iacocca Professorship. P.R., S.R.-S., and T.K.B. were supported by the NIH (GM62891) and the Beatson and Myra Reinhard Family Foundations. T.T. and J.L.K. were supported by grants from the NIH (AG13925 and AG31736) and the Ted Nash Long Life Foundation and the Noaber Foundation Professorship in Aging Research. M.A.M., P.R., J.L.K., T.K.B., and C.R.K. conceived and designed the experiments. M.A.M., P.R., T.T., J.B., S.R.-S., Y.M., and S.J.R. performed the experiments. All authors analyzed the data and edited/reviewed the manuscript. M.A.M., P.R., T.T., T.K.B., and C.R.K. wrote the manuscript. ",
year = "2012",
month = sep,
day = "5",
doi = "10.1016/j.cmet.2012.07.017",
language = "English (US)",
volume = "16",
pages = "336--347",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}