Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

被引:203
作者
Demontis, Fabio [1 ,2 ]
Piccirillo, Rosanna [3 ,4 ]
Goldberg, Alfred L. [3 ]
Perrimon, Norbert [1 ,5 ]
机构
[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[2] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Div Dev Biol, Memphis, TN 38105 USA
[3] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA
[4] IRCCS Mario Negri Inst Pharmacol Res, Dept Oncol, I-20156 Milan, Italy
[5] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA
关键词
DNA DELETION MUTATIONS; AGE-RELATED-CHANGES; MITOCHONDRIAL PROTEIN-SYNTHESIS; HYDROGEN-PEROXIDE RELEASE; NUCLEAR-PORE COMPLEXES; OXIDATIVE STRESS; CALORIE RESTRICTION; DIETARY RESTRICTION; ELECTRON-TRANSPORT; FLIGHT-MUSCLE;
D O I
10.1242/dmm.012559
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A characteristic feature of aged humans and Other mammals is the debilitating, progressive loss of Skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that; sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of Muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during; muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.
引用
收藏
页码:1339 / 1352
页数:14
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