Overexpression of PGC-1 alpha in aging muscle enhances a subset of young-like molecular patterns

Autor(es)

Garcia, Sofia ^[1] ; Nissanka, Nadee ^[2] ; Mareco, Edson A. ^[3] ; Rossi, Susana ^[4] ; Peralta, Susana ^[1] ; Diaz, Francisca ^[1] ; Rotundo, Richard L. ^{[2, 4]} ; Carvalho, Robson F. ^[5] ; Moraes, Carlos T. ^{[2, 4, 1]}

Afiliação do(s) autor(es)

^[1] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 - USA

^[2] Univ Miami, Miller Sch Med, Neurosci Grad Program, Miami, FL 33136 - USA

^[3] Univ Western Sao Paulo, Grad Program Environm & Reg Dev, Presidente Prudente - Brazil

^[4] Univ Miami, Miller Sch Med, Dept Cell Biol, Miami, FL 33136 - USA

^[5] Sao Paulo State Univ UNESP, Inst Biosci, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AGING CELL; v. 17, n. 2 APR 2018.
• Citações Web of Science: 11

Resumo

PGC-1 alpha is a transcriptional co-activator known as the master regulator of mitochondrial biogenesis. Its control of metabolism has been suggested to exert critical influence in the aging process. We have aged mice overexpressing PGC-1 alpha in skeletal muscle to determine whether the transcriptional changes reflected a pattern of expression observed in younger muscle. Analyses of muscle proteins showed that Pax7 and several autophagy markers were increased. In general, the steady-state levels of several muscle proteins resembled that of muscle from young mice. Age-related mtDNA deletion levels were not increased by the PGC-1 alpha-associated increase in mitochondrial biogenesis. Accordingly, age-related changes in the neuromuscular junction were minimized by PGC-1 alpha overexpression. RNA-Seq showed that several genes overexpressed in the aged PGC-1 alpha transgenic are expressed at higher levels in young when compared to aged skeletal muscle. As expected, there was increased expression of genes associated with energy metabolism but also of pathways associated with muscle integrity and regeneration. We also found that PGC-1 alpha overexpression had a mild but significant effect on longevity. Taken together, overexpression of PGC-1 alpha in aged muscle led to molecular changes that resemble the patterns observed in skeletal muscle from younger mice. (AU)

• Processo FAPESP: 12/13961-6 - Perfil genômico de RNAs mensageiros e microRNAs em células musculares esqueléticas tratadas in vitro com TNF-alfa e IFN-gama
• Beneficiário: Robson Francisco Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Regular