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Effects of caloric restriction mediated by SIRT3 in the aerobic and anaerobic capacities of mice: relations with the spontaneous activity, metabolic parameters and muscle mitochondrial function in aging process

Grant number: 15/00272-6
Support type:Scholarships abroad - Research
Effective date (Start): August 01, 2015
Effective date (End): June 15, 2016
Field of knowledge:Health Sciences - Physical Education
Principal researcher:Fúlvia de Barros Manchado Gobatto
Grantee:Fúlvia de Barros Manchado Gobatto
Host: Tomas Alberto Prolla
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Research place: University of Wisconsin-Madison (UW-Madison), United States  


The caloric restriction diet (CR) seems to be an effective strategy to improve mitochondrial function and thereby reduce the physiological declines associated to the aging process in organisms. However, the beneficial effects of CR are dependent of sirtuin 3 (SIRT3), a deacetylase protein present in the intramitochondrial membrane. Among the aspects that reduce with aging and impair the quality of life there are the aerobic and anaerobic capacities and the spontaneous activity of rodents, which might be softened by CR mediates by SIRT3. Accordingly, the main aim of this project is to investigate the effects of calorie restriction mediated by SIRT3 in the aerobic and anaerobic capacities of mice as well as its relationship with the spontaneous activity, metabolic parameters and muscle mitochondrial function in aging process. We will study male mice of C57BL/6 and mice that do not express the SIRT3 gene submitted to CR or diet control condition. To analyze the aging process, the experiments will be performed in eight groups of three different ages: young (5 months), middle-aged (15 months) and old (30 months). The evaluation of aerobic and anaerobic capacities will be held using the critical velocity protocol, from the application of 4 random run efforts on a treadmill running (intensities 18, 21, 24 and 27 m/min) and the time limit for each effort will be recorded. From these data, the linear model 'intensity vs. 1/ time limit" will be applied to obtain the y -intercept and the slope of fit, respectively, the CV (critical velocity - aerobic capacity) and anaerobic running capacity (ARC). Also, during the experimental procedure (at two moments), the spontaneous activity of all groups will be measured using a gravimetric system, with signs of strength being obtained for 23 hours with high capture rate signal. After the intervention, the animals will be euthanized for the extraction of muscle tissues (gastrocnemious, soleous and quadriceps) to determine the glycogen stores. Blood aliquots will be stored for following measurements of glucose, lipid profile (triglycerides, LDL, HDL, FFA and total cholesterol), total proteins, albumin, urea, creatinine and creatine kinase. The mithocondrial function will be measured with a high-resolution respirometer system Oxygraph2k (Oroboros Instruments, Austria), without being necessary mitochondrial isolation techniques. For comparison among groups ANOVA-three way will be applied considering the effects of age, diet and the presence of the SIRT3 gene. If necessary, posthoc Newman Keuls analysis will be used. We hope to identify whether the CR-mediated by SIRT3 is able to minimize the declines in aerobic and anaerobic capacity and spontaneous activity during aging process, and even the physiological mechanisms which may be associated to these potential benefits. (AU)

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Scientific publications (5)
(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)
RODRIGUES, NATALIA ALMEIDA; GOBATTO, CLAUDIO ALEXANDRE; MAIA FORTE, LUCAS DANTAS; DE BARROS SOUSA, FILIPE ANTONIO; TORSONI, ADRIANA SOUZA; DE FANTE, THAIS; MANCHADO-GOBATTO, FULVIA BARROS. Load-matched acute and chronic exercise induce changes in mitochondrial biogenesis and metabolic markers. APPLIED PHYSIOLOGY NUTRITION AND METABOLISM, v. 46, n. 10, p. 1196-1206, OCT 2021. Web of Science Citations: 0.
SCARIOT, PEDRO P. M.; MANCHADO-GOBATTO, FULVIA B.; VAN GINKEL, PAUL R.; PROLLA, TOMAS A.; GOBATTO, CLAUDIO A. Aerobic training associated with an active lifestyle exerts a protective effect against oxidative damage in hypothalamus and liver: The involvement of energy metabolism. Brain Research Bulletin, v. 175, p. 116-129, OCT 2021. Web of Science Citations: 0.
POLISEL, EMANUEL E. C.; BECK, WLADIMIR R.; SCARIOT, PEDRO P. M.; PEJON, TACIANE M. M.; GOBATTO, CLAUDIO A.; MANCHADO-GOBATTO, FULVIA B. Effects of high-intensity interval training in more or less active mice on biomechanical, biophysical and biochemical bone parameters. SCIENTIFIC REPORTS, v. 11, n. 1 MAR 19 2021. Web of Science Citations: 0.
MENEZES SCARIOT, PEDRO PAULO; MANCHADO-GOBATTO, FULVIA B.; PROLLA, TOMAS A.; MASSELLI DOS REIS, IVAN G.; GOBATTO, CLAUDIO ALEXANDRE. Housing conditions modulate spontaneous physical activity, feeding behavior, aerobic running capacity and adiposity in C57BL/6J mice. Hormones and Behavior, v. 115, SEP 2019. Web of Science Citations: 0.
RODRIGUES, NATALIA ALMEIDA; TORSONI, ADRIANA SOUZA; FANTE, THAIS; GUSTAVO, IVAN; DOS REIS, MASSELLI; GOBATTO, CLAUDIO ALEXANDRE; MANCHADO-GOBATTO, FULVIA BARROS. Lactate minimum underestimates the maximal lactate steady-state in swimming mice. APPLIED PHYSIOLOGY NUTRITION AND METABOLISM, v. 42, n. 1, p. 46-52, JAN 2017. Web of Science Citations: 3.

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