Overexpression of PGC ‐1α in aging muscle enhances a subset of young‐like molecular patterns
Open accessAbstract
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.
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Some of the anti-ageing effects of Parkin overexpression may have been mediated by its impact on PGC-1α content in old muscles.
“it is possible that some of the anti‐ageing effects of Parkin overexpression were mediated by its impact on PGC‐1α content in old muscles.”
From Parkin overexpression protects from ageing‐related loss of muscle mass and strength (2019) · cites this paper as Garcia et al. 2018
The Discussion reports that overexpressing PGC-1α in aged mouse muscle produced molecular features resembling younger muscle and was associated with a modest lifespan extension. The paper does not examine Parkin overexpression, its effect on PGC-1α content, or whether PGC-1α mediated Parkin’s effects. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOverexpression of PGC-1α increases mitochondrial protein content and antioxidant enzyme activity, modifies gene expression, attenuating the impact of aging on muscle tissue.
“Overexpression of PGC-1α increases mitochondrial protein content and antioxidant enzyme activity, in addition to modifying gene expression, thereby attenuating the impact of aging on muscle tissue [50,51].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [50]
Overexpression of PGC-1α can mitigate the effects of aging on muscle by increasing mitochondrial protein content and antioxidant enzyme activity and altering gene expression to resemble a youthful transcriptome profile.
“In contrast, overexpression of PGC-1α can mitigate the effects of aging on muscle by increasing mitochondrial protein content and antioxidant enzyme activity and altering gene expression to resemble a youthful transcriptome profile (79, 80).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [79]
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- Authors
- Garcia, S., Nissanka, N., Mareco, E. A., Rossi, S., Peralta, S., Diaz, F., Rotundo, R. L., Carvalho, R. F., & Moraes, C. T.
- Affiliations
- Department of Neurology University of Miami Miller School of Medicine Miami FL USA
- University of Miami (US)
- Universidade do Oeste Paulista (BR)
- Universidade Estadual Paulista (Unesp) (BR)
- Corresponding author
- Carvalho, Robson F.
- Moraes, Carlos T.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2018-02-10
- Volume
- 17
- Issue
- 2
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5847875
- OpenAlex
- W2790231778
- Cited by
- 81
- References
- 49
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 9 · 2023: 15 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 4
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- National Eye Institute (5R01EY010804)
- National Institute on Aging (1R01AG036871)
- Muscular Dystrophy Association
- Fundação de Amparo à Pesquisa do Estado de São Paulo (12/13961‐6)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- PGC-1α, skeletal muscle aging, mitochondrial biogenesis, transgenic mice, Pax7, autophagy, mitochondrial DNA deletions, neuromuscular junction, energy metabolism, muscle regeneration, longevity, transcriptional coactivator
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Female, Humans, Longevity, Male, Muscle Proteins, Transcription Factors, Muscle, Skeletal, Mice
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