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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis and function. Here, we combined bioinformatics, physiological, and molecular analyses to examine the role of mitonuclear imbalance and UPRmt in the skeletal muscle of aged rodents and humans. The analysis of transcripts from the skeletal muscle of aged humans (60-70 years old) revealed that individuals with higher levels of UPRmt-related genes displayed a consistent increase in several mitochondrial-related genes, including the OXPHOS-associated genes. Interestingly, high-intensity interval training (HIIT) was effective in stimulating the mitonuclear imbalance and UPRmt in the skeletal muscle of aged mice. Furthermore, these results were accompanied by higher levels of several mitochondrial markers and improvements in physiological parameters and physical performance. These data indicate that the maintenance or stimulation of the mitonuclear imbalance and UPRmt in the skeletal muscle could ensure mitochondrial proteostasis during aging, revealing new insights into targeting mitochondrial metabolism by using physical exercise.
Univ Estadual Campinas, Lab Mol Biol Exercise, Limeira, SP, Brazil
Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, SP, Brazil
Univ Estadual Campinas, Lab Funct Properties Foods, Limeira, SP, Brazil
Univ Sao Paulo, Postgrad Program Rehabil & Funct Performance, Ribeirao Preto, SP, Brazil
Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP, Brazil
Univ Estadual Campinas, Lab Nutr Genom, Limeira, SP, Brazil
Univ Campinas UNICAMP, CEPECE Ctr Res Sport Sci, Sch Appl Sci, Limeira, SP, Brazil
Univ Campinas UNICAMP, Fac Med Sci, Dept Internal Med, Campinas, SP, Brazil
Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, SP, Brazil
CNPq: 304771/2017-1
CNPq: 401189/2016-3
CAPES: 001
FAPESP: 2011/09656-0
FAPESP: 2018/07634-9
