McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Gerontology. 2017;63(6):580-589. doi: 10.1159/000479278. Epub 2017 Aug 17.
Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.
肌肉减少症是一种复杂的多因素疾病,包括肌肉纤维数量、结构和生理学的减少,以及与年龄相关的肌肉质量损失,并与力量下降、脆弱性增加、骨折和跌倒风险增加有关。治疗选择并不理想,包括运动和营养作为治疗的基石。目前的治疗原则包括识别和改变风险因素以预防疾病,但这些努力对目前受肌肉减少症影响的老年人的价值有限。开发新的有效的肌肉减少症治疗方法具有挑战性。潜在的治疗方法可以针对一个或多个提出的多种病因,如肌肉再生能力的丧失、生长激素、IGF-1、肌肉生长抑制素和其他内分泌信号分子等信号分子的年龄相关变化,以及去神经和线粒体功能障碍等与年龄相关的肌肉生理学变化。本文综述了旨在恢复足够的骨骼肌结构和功能的再生医学策略,包括外源性细胞输送和诱导成肌分化或逆转导致疾病的生理变化的药物治疗。本文讨论了改变微环境以提供有利于逆转和缓解疾病的环境的方法,这是一种潜在的再生医学方法。