Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction

• Published in: Mechanisms of ageing and development 2009-04, Vol.130 (4), p.272-280
• Main Authors: Marzetti, Emanuele, Carter, Christy S., Wohlgemuth, Stephanie E., Lees, Hazel A., Giovannini, Silvia, Anderson, Barbara, Quinn, LeBris S., Leeuwenburgh, Christiaan
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Apoptosis; Biological and medical sciences; Body Weight; Caloric Restriction; Calorie restriction; Caspases - metabolism; Development. Metamorphosis. Moult. Ageing; Fundamental and applied biological sciences. Psychology; Interleukin-15; Interleukin-15 - metabolism; Male; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Organ Size; Protein Subunits - metabolism; Rats; Receptors, Death Domain - metabolism; Receptors, Interleukin-15 - metabolism; Sarcopenia; Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2008.12.008

TNF-α-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-α-triggered apoptosis. We investigated IL-15 signaling and the TNF-α-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 α-chain decreased in senescent ad libitum (AL) fed rats, but were maintained in CR rodents. Elevations of TNF-α, 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-α-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.