Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats

Abstract

In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle.

Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles

“…Indeed, the observation that knockout or transgenic overexpression of IL-15 did not alter exercise or muscle phenotypes strengthens this possibility. Furthermore, previous reports have not been able to demonstrate consistently that increasing IL-15 levels in vivo exerts a significant therapeutic effect in skeletal muscle (11)(12)(13)34). However, reductions in soluble IL-15Rα in aged muscle were correlated with reductions in circulating IL-15 levels (6, 7).…”

“…In vitro experiments in myogenic cells initially suggested that IL-15 was an anabolic factor for skeletal muscle, able to stimulate the accumulation of contractile protein in differentiated myotubes (8)(9)(10). However, this result has not been replicated in vivo, as increasing IL-15 levels in wild-type experimental animals has not resulted in muscle hypertrophy, suggesting that IL-15 and IL-15Rα interactions in vivo may be more complex than simple ligand-receptor binding (11)(12)(13). Recently, studies have revealed differing neurological and locomotor activities when comparing IL-15Rα-KO, IL-15-KO, and IL-2Rβ-KO mice (14,15).…”

Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles

“…It should be noted that although the Bax levels were only slightly higher in RG compared with WG, much higher levels were observed in soleus compared with plantaris muscle (data not shown). In a report by Pistilli and Alway (54), the level of DNA fragmentation per milligram protein was higher in rat soleus relative to plantaris muscle; however, a direct comparison was not performed. This is consistent with our data showing significantly elevated levels of DNA fragmentation in RG compared with WG muscle.…”

Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats

“…This assay measures DNA fragmentation in myonuclei, satellite cells, and nonmuscle cell nuclei. However, because DNA fragmentation as determined by this ELISA is directly proportional to TUNEL identification of apoptotic muscle nuclei in old rat muscle after hindlimb suspension (33), the data obtained in the ELISA assay are a reasonable indicator of the apoptotic environment in skeletal muscle of the experimental animals.…”