Department of Aging and Geriatric Research, College of Medicine, Institute On Aging, Division of Biology of Aging, University of Florida, Gainesville, FL 32610, USA.
Exp Gerontol. 2010 Feb;45(2):138-48. doi: 10.1016/j.exger.2009.11.002. Epub 2009 Nov 10.
Sarcopenia, loss of muscle mass and function, is a common feature of aging. Oxidative damage and apoptosis are likely underlying factors. Autophagy, a process for the degradation of cellular constituents, may be a mechanism to combat cell damage and death. We investigated the effect of age on autophagy and apoptosis in plantaris muscle of male Fischer 344 rats that were either fed ad libitum, or mild, life-long calorie restricted (CR) alone or combined with life-long voluntary exercise. Upstream autophagy-regulatory proteins were either upregulated with age (Beclin-1) or unchanged (Atg7 and 9). LC3 gene and protein expression pattern as well as LAMP-2 gene expression, both downstream regulators of autophagy, however, suggested an age-related decline in autophagic degradation. Atg protein expression and LC3 and LAMP-2 gene expression were improved in CR rats with or without exercise. The age-related increase in oxidative damage and apoptosis were attenuated by the treatments. Both, oxidative damage and apoptosis correlated negatively with autophagy. We conclude that mild CR attenuates the age-related impairment of autophagy in rodent skeletal muscle, which might be one of the mechanisms by which CR attenuates age-related cellular damage and cell death in skeletal muscle in vivo.
肌肉减少症，即肌肉质量和功能的丧失，是衰老的一个常见特征。氧化损伤和细胞凋亡可能是其潜在的影响因素。自噬是一种细胞成分降解的过程，可能是对抗细胞损伤和死亡的机制。我们研究了年龄对雄性 Fischer 344 大鼠比目鱼肌自噬和凋亡的影响，这些大鼠分为自由进食组、轻度、终生热量限制（CR）组、终生热量限制加自愿运动组。自噬调节蛋白上游（Beclin-1）随年龄上调或不变（Atg7 和 9）。然而，LC3 基因和蛋白表达模式以及自噬下游调节因子 LAMP-2 基因表达均表明自噬降解随年龄而下降。CR 处理，无论是否有运动，均可改善 Atg 蛋白表达以及 LC3 和 LAMP-2 基因表达。这些处理还可减弱与年龄相关的氧化损伤和细胞凋亡的增加。氧化损伤和细胞凋亡与自噬呈负相关。我们的结论是，轻度 CR 可减轻啮齿动物骨骼肌与年龄相关的自噬损伤，这可能是 CR 减轻体内骨骼肌与年龄相关的细胞损伤和细胞死亡的机制之一。
