Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction.
Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction.
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DOI：
10.1016/j.mad.2008.12.008
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发表时间：
2009-04
影响因子：
5.3
通讯作者：
Leeuwenburgh C
中科院分区：
文献类型：
--
作者：
Marzetti E;Carter CS;Wohlgemuth SE;Lees HA;Giovannini S;Anderson B;Quinn LS;Leeuwenburgh C
TNF-α-介导的细胞凋亡在老年啮齿动物肌肉中增强，提示该途径可能参与了肌肉减少症。白介素-15 （IL-15）是一种肌肉来源的合成代谢细胞因子，可减轻病毒质大鼠的肌肉萎缩和细胞凋亡。这种作用被认为是通过抑制TNF-α-引发的细胞凋亡而发生的。我们研究了8、18、29和37月龄Fischer344×Brown挪威大鼠腓肠肌中IL-15信号通路和TNF-α-介导的细胞凋亡途径，与终生卡路里限制（CR，减少40%卡路里摄入）有关。衰老引起肌肉质量下降和细胞凋亡DNA片段增加，CR可减轻这一现象。随意喂养的衰老大鼠IL-15蛋白水平和IL-15受体α-链mRNA丰度下降，而CR则维持不变。在老年AL大鼠中观察到TNF-α、TNF受体1、cleaved caspase-8和-3的升高。我们的研究结果表明，衰老与大鼠腓肠肌中IL-15信号的减少有关，这可能部分通过TNF-α-介导的细胞凋亡的增强而导致肌肉减少。因此，CR对IL-15信号的保存可能代表了这种饮食干预骨骼肌抗衰老作用的进一步机制。
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 Fischer344×Brown 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.
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影响因子：
11.4
作者：
GIRI, JG;KUMAKI, S;ANDERSON, DM
通讯作者：
ANDERSON, DM
影响因子：
56.9
作者：
GRABSTEIN, KH;EISENMAN, J;GIRI, JG
通讯作者：
GIRI, JG
影响因子：
3.4
作者：
Malmgren, LT;Jones, CE;Bookman, LM
通讯作者：
Bookman, LM
DOI：
10.1152/ajpregu.2000.279.4.r1165
发表时间：
2000-10-01
影响因子：
2.8
作者：
Li, YP;Reid, MB
通讯作者：
Reid, MB
DOI：
10.1152/ajpregu.00576.2004
发表时间：
2005-05-01
影响因子：
2.8
作者：
Leeuwenburgh, C;Gurley, CM;Dupont-Versteegden, EE
通讯作者：
Dupont-Versteegden, EE