Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism.
Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism.
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DOI：
10.1111/acel.12153
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发表时间：
2014-02
期刊：
影响因子：
7.8
通讯作者：
Walsh K
中科院分区：
文献类型：
--
作者：
Akasaki Y;Ouchi N;Izumiya Y;Bernardo BL;Lebrasseur NK;Walsh K
衰老与胰岛素抵抗的发展、肥胖症的增加以及组织和器官中异位脂肪沉积有关。从中年开始，随着糖酵解和快速抽动肌纤维的优先丢失，瘦肉量逐渐下降。然而，目前尚不清楚肌肉丢失和代谢功能障碍在多大程度上存在因果关系，或者它们是否是衰老过程中独立的附属现象。在这里，我们使用了一只骨骼肌特异的、有条件的转基因小鼠，表达了一种构成活性形式的Akt1，以检测在喂食标准低脂饮食的幼年动物和中年动物中，糖酵解、快速抽动肌肉生长的后果。Akt1转基因的激活导致选择性骨骼肌肥大，逆转了随着年龄增长而观察到的瘦肉量的减少。Akt1介导的肌肉质量的增加导致老年动物脂肪质量的减少和肝脏脂肪变性，并纠正了与年龄相关的葡萄糖代谢损害。这些结果表明，瘦肌肉质量的丧失是与年龄相关的代谢功能障碍发展的一个重要因素，保留或恢复快速/糖酵解肌肉的干预措施可能会推迟代谢性疾病的发生。
Aging is associated with the development of insulin resistance, increased adiposity, and accumulation of ectopic lipid deposits in tissues and organs. Starting in mid-life there is a progressive decline in lean muscle mass associated with the preferential loss of glycolytic, fast-twitch myofibers. However, it is not known to what extent muscle loss and metabolic dysfunction are causally related or whether they are independent epiphenomena of the aging process. Here, we utilized a skeletal-muscle-specific, conditional transgenic mouse expressing a constitutively active form of Akt1 to examine the consequences of glycolytic, fast-twitch muscle growth in young vs. middle-aged animals fed standard low-fat chow diets. Activation of the Akt1 transgene led to selective skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon aging. The Akt1-mediated increase in muscle mass led to reductions in fat mass and hepatic steatosis in older animals, and corrected age-associated impairments in glucose metabolism. These results indicate that the loss of lean muscle mass is a significant contributor to the development of age-related metabolic dysfunction and that interventions that preserve or restore fast/glycolytic muscle may delay the onset of metabolic disease.
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影响因子：
29
作者：
Izumiya, Yasuhiro;Hopkins, Teresa;Walsh, Kenneth
通讯作者：
Walsh, Kenneth
DOI：
10.1152/ajpendo.00359.2006
发表时间：
2007-02-01
影响因子：
5.1
作者：
Frost, Robert A.;Nystrom, Gerald J.;Lang, Charles H.
通讯作者：
Lang, Charles H.
DOI：
10.1073/pnas.1115813109
发表时间：
2012-02-21
影响因子：
11.1
作者：
Finley, Lydia W. S.;Lee, Jaewon;Haigis, Marcia C.
通讯作者：
Haigis, Marcia C.
影响因子：
3.3
作者：
Morris, RT;Spangenburg, EE;Booth, FW
通讯作者：
Booth, FW
影响因子：
7.7
作者：
He, J;Watkins, S;Kelley, DE
通讯作者：
Kelley, DE