Changes in IL-15 expression and death-receptor apoptotic signaling in rat  gastrocnemius muscle with aging and life-long calorie restriction.
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.
Marzetti
Emanuele
E
Department of Aging and Geriatric Research, Institute on Aging, Division of Biology of Aging, University of Florida, Gainesville, FL 32610-0143, USA. emarzetti@aging.ufl.edu
Carter
Christy S
CS
Wohlgemuth
Stephanie E
SE
Lees
Hazel A
HA
Giovannini
Silvia
S
Anderson
Barbara
B
Quinn
LeBris S
LS
Leeuwenburgh
Christiaan
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D031204:Caloric Restriction; D020169:Caspases / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D009929:Organ Size; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D053218:Receptors, Death Domain / Q000378:metabolism*; D053647:Receptors, Interleukin-15 / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019409:Interleukin-15; D021122:Protein Subunits; D053218:Receptors, Death Domain; D053647:Receptors, Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases