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Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics.
Campos, Juliane Cruz; Marchesi Bozi, Luiz Henrique; Krum, Barbara; Grassmann Bechara, Luiz Roberto; Ferreira, Nikolas Dresch; Arini, Gabriel Santos; Albuquerque, Rudá Prestes; Traa, Annika; Ogawa, Takafumi; van der Bliek, Alexander M; Beheshti, Afshin; Chouchani, Edward T; Van Raamsdonk, Jeremy M; Blackwell, T Keith; Ferreira, Julio Cesar Batista.
Afiliação
  • Campos JC; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Marchesi Bozi LH; Research Division, Joslin Diabetes Center, Boston, MA 02215.
  • Krum B; Department of Genetics, Harvard Medical School, Boston, MA 02215.
  • Grassmann Bechara LR; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Ferreira ND; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
  • Arini GS; Department of Cell Biology, Harvard Medical School, Boston, MA 02215.
  • Albuquerque RP; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Traa A; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Ogawa T; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • van der Bliek AM; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Beheshti A; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
  • Chouchani ET; Department of Neurology and Neurosurgery, McGill University, Montreal H3A 2B4, Canada.
  • Van Raamsdonk JM; Metabolic Disorders and Complications Program, and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal H4A 3J1, Canada.
  • Blackwell TK; Research Division, Joslin Diabetes Center, Boston, MA 02215.
  • Ferreira JCB; Department of Genetics, Harvard Medical School, Boston, MA 02215.
Proc Natl Acad Sci U S A ; 120(2): e2204750120, 2023 01 10.
Article em En | MEDLINE | ID: mdl-36595699
Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and fusion are critical effectors of mitochondrial plasticity, which allows a fine-tuned regulation of organelle connectiveness, size, and function. Here we have investigated the role of mitochondrial dynamics during exercise in the model organism Caenorhabditis elegans. We show that in body-wall muscle, a single exercise session induces a cycle of mitochondrial fragmentation followed by fusion after a recovery period, and that daily exercise sessions delay the mitochondrial fragmentation and physical fitness decline that occur with aging. Maintenance of proper mitochondrial dynamics is essential for physical fitness, its enhancement by exercise training, and exercise-induced remodeling of the proteome. Surprisingly, among the long-lived genotypes we analyzed (isp-1,nuo-6, daf-2, eat-2, and CA-AAK-2), constitutive activation of AMP-activated protein kinase (AMPK) uniquely preserves physical fitness during aging, a benefit that is abolished by impairment of mitochondrial fission or fusion. AMPK is also required for physical fitness to be enhanced by exercise, with our findings together suggesting that exercise may enhance muscle function through AMPK regulation of mitochondrial dynamics. Our results indicate that mitochondrial connectivity and the mitochondrial dynamics cycle are essential for maintaining physical fitness and exercise responsiveness during aging and suggest that AMPK activation may recapitulate some exercise benefits. Targeting mechanisms to optimize mitochondrial fission and fusion, as well as AMPK activation, may represent promising strategies for promoting muscle function during aging.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases Ativadas por AMP / Dinâmica Mitocondrial Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases Ativadas por AMP / Dinâmica Mitocondrial Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos