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Nr1d1 function on the aging-associated Sarcopenia

Grant number: 19/11820-5
Support type:Research Projects - Thematic Grants
Duration: August 01, 2021 - July 31, 2026
Field of knowledge:Health Sciences - Physical Education
Principal researcher:Adelino Sanchez Ramos da Silva
Grantee:Adelino Sanchez Ramos da Silva
Home Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Pesquisadores principais:
Ellen Cristini de Freitas ; José Rodrigo Pauli
Assoc. researchers:Dennys Esper Corrêa Cintra ; Donato A Rivas ; Eduardo Rochete Ropelle ; Ellen Cristini de Freitas ; Fernando Moreira Simabuco ; Giovana Rampazzo Teixeira ; José Rodrigo Pauli ; Leandro Pereira de Moura
Associated grant(s):21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories, AP.EMU
Associated scholarship(s):21/14233-3 - Effects of PGC-1alpha conditional deletion and exercise on mitochondrial biogenesis, autophagy and rev-erb-alpha pathways in mouse skeletal muscle: a proteomics approach, BP.PD
22/01957-6 - Effects of combined physical exercise on Notch and autophagy pathways in skeletal muscle in early aging animal model, BP.IC
22/01220-3 - The influence of aerobic exercise on myostatin expression and its relationship with Alzheimer's Disease in APP/PS1mice, BP.IC
+ associated scholarships 21/13847-8 - Effects of time-restricted feeding combined with physical exercise or REV-ERB agonist on obesity and liver metabolism of male and female mice, BP.MS
21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture, BP.PD
21/08693-1 - Effect of global or conditional deletion (skeletal muscle) of the Nr1d1 gene on aging, BP.PD - associated scholarships

Abstract

Recently, the World Health Organization classified Sarcopenia as a disease, which will allow the establishment of universal clinical guidelines for its diagnosis and treatment. In this sense, the rev-erb-alpha protein is a promising molecular target for the prevention and treatment of Sarcopenia, since it plays an essential role in the regulation of autophagy, mitochondrial content, oxidative function, and skeletal muscle mass maintenance. Therefore, the present thematic project will investigate the function of the gene nuclear receptor subfamily 1 group D member 1 (Nr1d1) in the development of Sarcopenia associated with aging through experiments on cells, rodents, and humans. For this, the following subprojects will be used: 1) effect of aging on Nr1d1 and its relationship with Sarcopenia; 2) effect of global or conditional deletion of Nr1d1 on aging; 3) interactome analysis of rev-erb-alpha protein through immunoprecipitation of the target protein and identification of possible ligands by mass spectrometry in cell culture; 4) effects of pharmacological, nutritional and genetic activation of Nr1d1 on the aging process; 5) effects of physical exercise on the aging-induced Sarcopenia: the role of rev-erb-alpha in the skeletal muscle. The methodologies used in this project will be RNA-seq, immunoblotting, Real time-RTqPCR, interactome, mass spectrometry, gene therapy (CRISPR/Cas9 and adeno-associated virus vector), histology, immunohistochemistry, immunofluorescence, bioinformatics, and lysosomal autophagy flow. According to the statistical distribution of the data, parametric or non-parametric tests will be used to compare the studied parameters between the experimental groups. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
AZEVEDO MACEDO, ANA PAULA; RAMOS DA SILVA, ADELINO SANCHEZ; MUNOZ, VITOR ROSETTO; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO. Mitochondrial dysfunction plays an essential role in remodeling aging adipose tissue. MECHANISMS OF AGEING AND DEVELOPMENT, v. 200, . (20/08192-0, 20/13443-1, 19/21709-4, 19/11820-5)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.