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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):23/16626-8 - Modulation of Rev-erb-alpha by global deletion of NLRP3., BP.PD
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
+ associated scholarships 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
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
22/09100-7 - Role of rev-erb-alpha in aging-associated endoplasmic reticulum stress, BP.DR
22/15670-0 - Scholarship TT5_Function of Nr1d1 on sarcopenia associated with aging., BP.TT
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


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)

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Scientific publications (11)
(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)
ABUD, GABRIELA FERREIRA; DE CARVALHO, FLAVIA GIOLO; BATITUCCI, GABRIELA; TRAVIESO, SOFIA GERMANO; BUENO JUNIOR, CARLOS ROBERTO; BARBOSA JUNIOR, FERNANDO; MARCHINI, JULIO SERGIO; DE FREITAS, ELLEN CRISTINI. Taurine as a possible antiaging therapy: A controlled clinical trial on taurine antioxidant activity in women ages 55 to 70. NUTRITION, v. 101, p. 8-pg., . (19/11820-5)
MUNOZ, VITOR ROSETTO; BOTEZELLI, JOSE DIEGO; GASPAR, RAFAEL CALAIS; DA ROCHA, ALISSON L.; VIEIRA, RENAN FUDOLI LINS; CRISOL, BARBARA MOREIRA; BRAGA, RENATA ROSSETO; SEVERINO, MATHEUS BRANDEMARTE; NAKANDAKARI, SUSANA CASTELO BRANCO RAMOS; ANTUNES, GABRIEL CALHEIROS; et al. Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4(+/-) mice. CELLULAR AND MOLECULAR LIFE SCIENCES, v. 80, n. 5, p. 16-pg., . (16/18488-8, 21/08692-5, 15/26000-2, 19/11820-5, 20/13443-1, 18/20872-6)
PINTO, ANA P.; MUNOZ, VITOR R.; DA ROCHA, ALISSON L.; ROVINA, RAFAEL L.; FERRARI, GUSTAVO D.; ALBERICI, LUCIANE C.; SIMABUCO, FERNANDO M.; TEIXEIRA, GIOVANA R.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; et al. IL-6 deletion decreased REV-ERB alpha protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise. FRONTIERS IN IMMUNOLOGY, v. 13, p. 13-pg., . (21/06291-3, 21/08693-1, 19/11820-5, 17/12765-2, 19/21709-4, 21/08692-5, 20/13443-1, 18/14818-9)
DA ROCHA, ALISSON L.; PINTO, ANA P.; BEDO, BRUNO L. S.; MORAIS, GUSTAVO P.; OLIVEIRA, LUCIANA C.; CAROLINO, RUITHER O. G.; PAULI, JOSE R.; SIMABUCO, FERNANDO M.; DE MOURA, LEANDRO P.; ROPELLE, EDUARDO R.; et al. Exercise alters the circadian rhythm of REV-ERB-alpha and downregulates autophagy-related genes in peripheral and central tissues. SCIENTIFIC REPORTS, v. 12, n. 1, p. 13-pg., . (21/08693-1, 19/17532-1, 17/25492-4, 19/11820-5, 17/19869-8, 17/12765-2)
MARAFON, BRUNO B.; PINTO, ANA P.; ROPELLE, EDUARDO R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; PAULI, JOSE R.; DA SILVA, ADELINO S. R.. Muscle endoplasmic reticulum stress in exercise. ACTA PHYSIOLOGICA, v. 235, n. 1, p. 13-pg., . (21/08693-1, 20/04269-8, 19/11820-5)
DE SOUSA NETO, IVO VIEIRA; QUAGLIOTTI DURIGAN, JOAO LUIZ; RAMOS DA SILVA, ADELINO SANCHEZ; MARQUETI, RITA DE CASSIA. Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches. BIOLOGY-BASEL, v. 11, n. 5, p. 22-pg., . (19/11820-5)
PINTO, ANA P.; MUNOZ, VITOR R.; TAVARES, MARIA EDUARDA A.; DOS SANTOS, JONATHAS R.; REBELO, MACARIO A.; ALBERICI, LUCIANE C.; SIMABUCO, FERNANDO M.; TEIXEIRA, GIOVANA R.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; et al. Combined physical exercise reverses the reduced expression of Bmal1 in the liver of aged mice. Life Sciences, v. 312, p. 12-pg., . (21/08693-1, 21/08692-5, 20/13443-1, 21/06291-3, 19/11820-5)
BRICOLA, RAFAEL S.; CORDEIRO, ANDRE, V; CRISOL, BARBARA M.; BRAGA, RENATA R.; DE MELO, DIEGO G.; ROCHA, MATHEUS B.; GASPAR, RAFAEL C.; NAKANDAKARI, SUSANA C. B. R.; SILVA, VAGNER R. R.; ANARUMA, CHADI P.; et al. Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise. Cell Biochemistry and Function, v. N/A, p. 10-pg., . (19/21709-4, 18/03122-3, 19/11820-5)
MARAFON, BRUNO B.; PINTO, ANA P.; DE VICENTE, LARISSA G.; DA ROCHA, ALISSON L.; SIMABUCO, FERNANDO M.; ROPELLE, EDUARDO R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; PAULI, JOSE R.; DA SILVA, ADELINO S. R.. Genetic ablation of Toll-like Receptor 4 seems to activate the apoptosis pathway in the skeletal muscle of mice after acute physical exercise. Cell Biochemistry and Function, v. N/A, p. 12-pg., . (20/13443-1, 20/04269-8, 19/11820-5, 21/06291-3)
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)
MUNOZ, V. R.; GASPAR, R. C.; MANCINI, M. C. S.; DE LIMA, R. D.; VIEIRA, R. F. L.; CRISOL, B. M.; ANTUNES, G. C.; TROMBETA, J. C. S.; BONFANTE, I. L. P.; SIMABUCO, F. M.; et al. Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents. Journal of Endocrinological Investigation, v. N/A, p. 13-pg., . (16/18488-8, 19/11820-5, 18/20872-6, 21/08692-5, 20/13443-1, 15/26000-2)

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