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Skeletal muscle autophagy and its role in sarcopenia and organismal aging
Abstract
Sarcopenia, the loss of skeletal muscle mass and strength in the aged, is an important medical condition but its etiology is incompletely understood. Because autophagy promotes myofiber atrophy in the young, it was believed that autophagy inhibition would prevent sarcopenia. However, recent studies have revealed that autophagy actually maintains muscle mass and that its function declines during muscle aging. Consistently, boosting basal autophagy protects from age-related muscle dysfunction by promoting the selective degradation of misfolded proteins and dysfunctional organelles. Conversely, autophagy inhibition leads to loss of muscle strength and induces a maladaptive stress response responsible for myofiber atrophy in the aged. In addition to cell-autonomous effects, muscle autophagy and associated signaling pathways induce systemic responses in other aging tissues by modulating the expression and secretion of myokines. We propose that myokines and pharmacologic interventions that boost selective autophagy may prevent sarcopenia, delay systemic aging, and extend health span.
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“Increasing evidence has demonstrated that the imbalance of protein synthesis and protein degradation during the aging process can lead to the declined mass of skeletal muscle, a common occurrence in senile muscular atrophy [27].”
From Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway (2021) · cites this paper as [27]
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Metadata
- Authors
- Jiao, J., & Demontis, F.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Demontis, Fabio
- ORCID
- Demontis, Fabio
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 34
- Pages
- 1-6
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2605686103
- Cited by
- 184
- References
- 56
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 25 · 2023: 22 · 2022: 22 · 2021: 29 · 2020: 24 · 2019: 21 · 2018: 6 · 2017: 5
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- American Federation for Aging Research
- Glenn Foundation for Medical Research, the Hartwell Foundation
- American Parkinson Disease Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- sarcopenia, biological aging, muscle fiber atrophy, selective autophagy, myokines, misfolded protein degradation, healthspan, autophagy inhibition
- MeSH terms
- Aging, Animals, Autophagy, Humans, Muscle, Skeletal, Intercellular Signaling Peptides and Proteins, Sarcopenia
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