Nr1d1 function on the aging-associated Sarcopenia

• Grant number: 19/11820-5
• Support Opportunities: Research Projects - Thematic Grants
• Duration: August 01, 2021 - July 31, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Adelino Sanchez Ramos da Silva
• Host 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
• Associated 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): 23/01611-5 - Evaluation of the DNA methylation pattern in healthy, sarcopenic, obese and obese sarcopenic older adults: a cross-cross-cross study, AP.R; 21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories, AP.EMU
• Associated scholarship(s): 22/12708-7 - Analysis of protein intake and its correlation with body composition and biochemical parameters in elderly women with sarcopenic obesity submitted to physical exercise., BP.IC; 22/06638-6 - Metabolic and molecular responses under the effect of taurine supplementation with and without multicomponent training in elderly women with sarcopenic obesity using the metabolomics approach., BP.DR; 23/02774-5 - Taurine supplementation associated or not with multicomponent training: Effect on browning of white adipose tissue and metabolic and molecular responses using the metabolomics approach in elderly women with sarcopenic obesity, BP.TT; + associated scholarships 22/14758-1 - Implications of time-restricted feeding combined with resistance exercise or Reverb agonist on hepatic metabolism and circadian cycle in mice fed a high-fat diet, BP.MS; 22/15670-0 - Scholarship TT5_Function of Nr1d1 on sarcopenia associated with aging., BP.TT; 22/09100-7 - Role of rev-erb-alpha in aging-associated endoplasmic reticulum stress, BP.DR; 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; 22/00221-6 - Taurine supplementation associated or not with physical exercise: effect on the browning of white adipose tissue in elderly women with Sarcopenic Obesity, BP.DD; 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; 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)

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, DEC 2021. (20/08192-0, 20/13443-1, 19/21709-4, 19/11820-5)