Overexpression of PGC-1α in aging muscle enhances a subset of young-like molecular patterns.
| Title: | Overexpression of PGC-1α in aging muscle enhances a subset of young-like molecular patterns. |
|---|---|
| Authors: | Garcia S; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; Nissanka N; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA.; Mareco EA; Graduate Program in Environment and Regional Development, University of Western São Paulo, Presidente Prudente, Brazil.; Rossi S; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, USA.; Peralta S; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; Diaz F; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; Rotundo RL; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, USA.; Carvalho RF; Institute of Biosciences, São Paulo State University (UNESP), Botucatu, Brazil.; Moraes CT; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA.; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, USA. |
| Source: | Aging cell [Aging Cell] 2018 Apr; Vol. 17 (2). Date of Electronic Publication: 2018 Feb 10. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Wiley-Blackwell; Original Publication: Oxford, UK : Blackwell Pub., c2002- |
| MeSH Terms: | Muscle Proteins/*metabolism ; Muscle, Skeletal/*metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*metabolism ; Transcription Factors/*metabolism; Aging ; Animals ; Female ; Humans ; Longevity ; Male ; Mice |
| Abstract: | PGC-1α 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-1α 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-1α-associated increase in mitochondrial biogenesis. Accordingly, age-related changes in the neuromuscular junction were minimized by PGC-1α overexpression. RNA-Seq showed that several genes overexpressed in the aged PGC-1α 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-1α overexpression had a mild but significant effect on longevity. Taken together, overexpression of PGC-1α in aged muscle led to molecular changes that resemble the patterns observed in skeletal muscle from younger mice.; (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.) |
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| Grant Information: | P30 EY014801 United States EY NEI NIH HHS; R01 AG036871 United States AG NIA NIH HHS; R01 EY010804 United States EY NEI NIH HHS; R01 NS079965 United States NS NINDS NIH HHS |
| Contributed Indexing: | Keywords: aging; lifespan; longevity; mitochondria; mouse models; skeletal muscle |
| Substance Nomenclature: | 0 (Muscle Proteins); 0 (PPARGC1A protein, human); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 0 (Transcription Factors) |
| Entry Date(s): | Date Created: 20180211 Date Completed: 20190830 Latest Revision: 20240922 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5847875 |
| DOI: | 10.1111/acel.12707 |
| PMID: | 29427317 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't