Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 130, Issue 4, Pages 272-280Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2008.12.008
Keywords
Sarcopenia; Interleukin-15; Tumor necrosis factor-alpha; Calorie restriction; Apoptosis
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Funding
- USDA Cooperative State Research, Education, and Extension Service Animal Growth and Nutrient Utilization Program [2005-35206-15264]
- Department of Veterans Affairs
- University of Florida Institute
- Claude D. Pepper Older Americans Independence Center [1 P30 AG028740]
- [NIA R01-AG17994]
- [AG21042]
- [NIH R01-AG024526-02]
- [NIH R01-AG024136]
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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-a-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-a-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. Published by Elsevier Ireland Ltd.
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