Apoptosis in skeletal muscle with aging
Abstract
Sarcopenia may be partly due to a loss in total fiber number by apoptosis. We have investigated age-related alterations in the mitochondria-mediated pathway leading to apoptosis in the gastrocnemius muscle from 6-mo-old and 24-mo-old male Fisher 344 rats. Apoptosis (mono- and oligonucleosome fragmentation) in the gastrocnemius muscle was increased by 50% in the old rats compared with the adult animals. Furthermore, there was a significant correlation between cytosolic cytochrome c and caspase-3 activity, although neither cytochrome c nor caspase-3 activity increased significantly with age. Furthermore, there was a significant correlation between caspase-3 activity and mono- and oligonucleosome fragmentation in the old rats only. Mitochondrial Bcl-2 and Bax were not altered with age. In vitro experiments demonstrated that activation of the caspase cascade in skeletal muscle might be limited by procaspase-9 activation. This is the first study to explore the role of apoptosis in sarcopenia and suggests that subtle changes in apoptosis are involved.
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The mitochondrial permeability transition pore (mPTP) becomes dysfunctional in old rodents and humans.
“Several studies have also shown that the mitochondrial permeability transition pore (mPTP) becomes dysfunctional in old rodents and humans [9,12,13,14].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [12]
Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents and humans.
“Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents (4, 7, 26, 34, 47, 77, 88, 130), and humans (44, 145).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [34]
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References 45 · Cited by 377
- Authors
- Dirks, A., & Leeuwenburgh, C.
- Affiliations
- University of Florida Health (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2002-02-01
- Volume
- 282
- Issue
- 2
- Pages
- R519-R527
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2135817592
- Cited by
- 377
- References
- 45
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 23 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 8 · 2016: 17 · 2015: 16 · 2014: 11 · 2013: 13 · 2012: 20
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG17994-01, R01AG017994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- apoptosis, sarcopenia, skeletal muscle aging, gastrocnemius, mitochondrial apoptosis, cytochrome c, caspase-3, caspase-9, Bcl-2, Bax, muscle fiber loss, F344 rats
- MeSH terms
- Aging, Animals, Cytochrome c Group, Cytosol, Endonucleases, Free Radicals, Male, Mitochondria, Nucleosomes, Organ Size, Proteins, Proto-Oncogene Proteins, Rats, Inbred F344, Apoptosis, Oxidative Stress, Muscle, Skeletal, Proto-Oncogene Proteins c-bcl-2, Caspases, bcl-2-Associated X Protein, Rats, Caspase 3, Apoptotic Protease-Activating Factor 1, In Vitro Techniques
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