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Identification of mechanisms responsible for the beneficial effects of caloric restriction

Grant number: 12/04079-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2012
Effective date (End): May 31, 2015
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Bruna Brasil Brandao
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction, AP.JP


Calorie restriction promotes beneficial health effects and prolongs lifespan in diverse species, from yeast to primates. Our group recently identified an evolutionarily conserved phenomenon that is directly associated with the aging process and can be reversed by caloric restriction. This phenomenon is characterized by progressive dysfunction of the microRNAs processing pathway, particularly Dicer, in tissues responsible for the cell non-autonomous control of life expectancy, including the adipose tissue. We thus determined not only a mechanism by which organisms modulate the aging process, but also a biomarker that can be used to study the effects of caloric restriction in several species. The objective of this proposal is therefore to use this biomarker as readout, and integrating it with biochemical and metabolic parameters, to identify factors that contribute to the effects of caloric restriction on adipose tissue cells. To do this, we will carry out experiments in which we: 1) restrict specific components of the culture medium of preadipocytes, 2) incubate these cells with serum from animals treated with caloric restriction, and 3) pharmacologically interfere with important metabolic pathways of preadipocytes. We will also evaluate the processing of miRNAs themselves and the susceptibility to stress in these cells. Thus we seek to understand how the processing of miRNAs is regulated in adipose tissue in response to caloric restriction, aiming to propose interventions that could mimic its beneficial effects.

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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)
BRANDAO, BRUNA B.; MADSEN, SOREN; RABIEE, ATEFEH; OLIVERIO, MATTEO; RUIZ, GABRIEL P.; FERRUCCI, DANILO L.; BRANQUINHO, JESSICA L.; RAZOLLI, DANIELA; PINTO, SILAS; NIELSEN, THOMAS S.; et al. Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 38, p. 23932-23941, . (17/03423-0, 15/01316-7, 17/04377-2, 12/06238-6, 15/03292-8, 17/01184-9, 12/04079-8, 18/21635-8, 17/07975-8)
PEREIRA, CATIA M.; FILEV, RENATO; DUBIELA, FRANCISCO P.; BRANDAO, BRUNA B.; QUEIROZ, CLAUDIO M.; LUDWIG, RAISSA G.; HIPOLIDE, DEBORA; LONGO, BEATRIZ M.; MELLO, LUIZ E.; MORI, MARCELO A.; et al. The GCN2 inhibitor IMPACT contributes to diet-induced obesity and body temperature control. PLoS One, v. 14, n. 6, . (09/52047-5, 12/04079-8)

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