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The role of Dicer in adipose tissue in aging, stress response and in the effects of caloric restriction in mice

Grant number: 11/24109-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2013
Effective date (End): February 28, 2015
Field of knowledge:Health Sciences - Medicine
Principal researcher:Marcelo Alves da Silva Mori
Grantee:Felipe Castellani Gomes dos Reis
Home Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil
Associated research grant:10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction, AP.JP

Abstract

Aging and obesity are risk factors for multiple diseases, including type 2 diabetes, cancer and neurodegeneration. This risk can be decreased by calorie restriction, which also results in increased lifespan and improved response to stress in organisms from C. elegans to mammals. In previous work developed by Dr. Mori, shows that there is coordinated down-regulation of components of the miRNA processing pathway, especially Dicer, and multiple miRNAs in adipose tissue of mice and preadipocytes from humans with aging, and this can be prevented in mice by calorie restriction. This down-regulation of Dicer expression can be reproduced in cultured murine preadipocytes by exposure to environmental stressors, including oxidative stress and UV radiation. In C. elegans, Dicer and miRNA expression are also down-regulated with age, while overexpression of Dicer in the worm intestine, the analogue of the mammalian adipose tissue, confers increased lifespan and stress resistance. Thus, we have defined an important role for the miRNA processing in adipose tissue and its analogues in controlling longevity of an organism and its ability to handle environmental stress.To follow-up on these exciting data indicating a role for Dicer and miRNAs in fat in the aging process, we have created fat-specific Dicer knockout mice. The overarching goal of these studies is to understand how the regulation of the miRNA processing pathway in adipose tissue with age and caloric restriction impacts on aging, metabolism and stress response using this mouse model. Based on our preliminary data we hypothesize that Dicer knockout in adipose tissue will: 1) increase the expression of aging and senescence biomarkers in several tissues (adipo or non-adipocites) ; 2) prevent the beneficial effects of calorie restriction; and 3) promote age-associated diseases, including diabetes and insulin resistance, in mice. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
REIS, FELIPE C. G.; BRANQUINHO, JESSICA L. O.; BRANDAO, BRUNA B.; GUERRA, BEATRIZ A.; SILVA, ISMAEL D.; FRONTINI, ANDREA; THOMOU, THOMAS; SARTINI, LORIS; CINTI, SAVERIO; KAHN, C. RONALD; FESTUCCIA, WILLIAM T.; KOWALTOWSKI, ALICIA J.; MORI, MARCELO A. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice. AGING-US, v. 8, n. 6, p. 1201-1222, JUN 2016. Web of Science Citations: 16.

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