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Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction
Open accessAbstract
TNF-alpha-mediated apoptosis is enhanced in aged rodent muscles, suggesting that this pathway may be involved in sarcopenia. Interleukin-15 (IL-15), a muscle-derived anabolic cytokine, mitigates muscle wasting and apoptosis in cachectic rats. This effect is thought to occur through inhibition of TNF-alpha-triggered apoptosis. We investigated IL-15 signaling and the TNF-alpha-mediated pathway of apoptosis in the gastrocnemius muscle of Fischer344xBrown Norway rats across the ages of 8, 18, 29 and 37 months, in relation to life-long calorie restriction (CR, 40% calorie intake reduction). Aging caused loss of muscle mass and increased apoptotic DNA fragmentation, which were mitigated by CR. Protein levels of IL-15 and mRNA abundance of IL-15 receptor a-chain decreased in senescent ad libitum (AL) fed rats, but were maintained in CR rodents. Elevations of TNF-alpha, TNF-receptor 1, cleaved caspase-8 and -3 were observed at advanced age in AL rats. These changes were prevented or mitigated by CR. Our results indicate that aging is associated with decreased IL-15 signaling in rat gastrocnemius muscle, which may contribute to sarcopenia partly through enhanced TNF-alpha-mediated apoptosis. Preservation of IL-15 signaling by CR may therefore represent a further mechanism contributing to the anti-aging effect of this dietary intervention in skeletal muscle.
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“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 [88]
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Metadata
- Authors
- Marzetti, E., Carter, C. S., Wohlgemuth, S. E., Lees, H. A., Giovannini, S., Anderson, B., Quinn, L. S., & Leeuwenburgh, C.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- University of Florida (US)
- University of Washington (US)
- Corresponding author
- Marzetti, Emanuele
- Leeuwenburgh, Christiaan
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 130
- Issue
- 4
- Pages
- 272-280
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC2768529
- OpenAlex
- W1999472449
- Cited by
- 113
- References
- 65
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 13
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Funders
- National Institute on Aging (R01AG024136, R01AG024526, R01AG017994, AG-21042, R01AG021042, P30AG028740)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- IL-15, caloric restriction, muscle aging, sarcopenia, TNF-α, apoptosis, death receptor signaling, gastrocnemius, skeletal muscle, caspase-8, caspase-3, TNF receptor 1, muscle atrophy, anti-aging diet
- MeSH terms
- Aging, Animals, Body Weight, Male, Organ Size, Tumor Necrosis Factor-alpha, Signal Transduction, Apoptosis, Muscle, Skeletal, Interleukin-15, Caspases, Protein Subunits, Caloric Restriction, Rats, Receptors, Death Domain, Receptors, Interleukin-15
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