| Literature DB >> 19396981 |
Emanuele Marzetti1, Christy S Carter, Stephanie E Wohlgemuth, Hazel A Lees, Silvia Giovannini, Barbara Anderson, LeBris S Quinn, Christiaan Leeuwenburgh.
Abstract
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.Entities:
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Year: 2009 PMID： 19396981 PMCID： PMC2768529 DOI： 10.1016/j.mad.2008.12.008
Source DB: PubMed Journal: Mech Ageing Dev ISSN： 0047-6374 Impact factor: 5.432