Characterization in mice of novel genes involved in the evolutionarily conserved m...
| Grant number: | 15/01316-7 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2015 - August 31, 2017 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Principal Investigator: | Marcelo Alves da Silva Mori |
| Grantee: | Marcelo Alves da Silva Mori |
| Home Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Assoc. researchers: | Fernanda Marques da Cunha ; William Tadeu Lara Festuccia |
Abstract
Aging is one of the main risk factors for chronic diseases and has been increasing in prevalence worldwide in the past few decades. Advances in the understanding of the mechanisms involved in the aging process and how interventions can delay or prevent its deleterious consequences are thus becoming urgent. Health span can be increased in different species, including in primates, by metabolic interventions such as caloric restriction and exercise. The mechanisms through which these interventions slow down age-related functional decline are not yet clear but appear to involve metabolic processes that have the mitochondria as their main regent. Our data show that there is a coordinated reduction in the expression of components of the miRNA processing pathway, particularly the enzyme Dicer, and several miRNAs in adipose tissue of mice, in human preadipocytes and in the nematode C. elegans with aging, and this reduction is prevented in mice and C. elegans by caloric restriction. In C. elegans, overexpression of Dicer in the intestine of the worm, the functional analogue of the adipose tissue of mammals, results in increased life span and increased resistance to oxidative and metabolic stress. In recent data from our group, we observed that Dicer knockdown reduces respiration in nematodes and significantly decreases the expression of genes involved in mitochondrial biogenesis and function in adipose tissue of mice. In addition, worms that do not express Dicer have blocked the effects of increased life span promoted by calorie restriction or treatment with Metformin, which depend on an adaptive mitochondrial response. According to these data, we propose a more detailed study of these mechanisms, using different genetically modified animal models to assess whether Dicer and certain miRNAs are capable of regulating life span and/or determine some of the beneficial effects of caloric restriction by controlling essential metabolic functions involving the mitochondria. (AU)