Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
Department of General medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
Theranostics. 2021 Mar 31;11(12):5675-5685. doi: 10.7150/thno.46436. eCollection 2021.
Aging frailty is a complex geriatric syndrome that becomes more prevalent with advancing age. It constitutes a major health problem due to frequent adverse outcomes. Frailty is characterized by disruption of physiological homeostasis and progressive decline of health status. Multiple factors contribute to development of frailty with advancing age, including genome instability, DNA damage, epigenetic alternations, stem cell exhaustion, among others. These interrelated factors comprehensively result in loss of tissue homeostasis and diminished reserve capacity in frailty. Therefore, the aged organism gradually represents symptoms of frailty with decline in physiological functions of organs. Notably, the brain, cardiovascular system, skeletal muscle, and endocrine system are intrinsically interrelated to frailty. The patients with frailty may display the diminished reserves capacity of organ systems. Due to the complex pathophysiology, no specific treatments have been approved for prevention of this syndrome. At such, effective strategies for intervening in pathogenic process to improve health status of frail patients are highly needed. Recent progress in cell-based therapy has greatly contributed to the amelioration of degenerative diseases related to age. Mesenchymal stem cells (MSCs) can exert regenerative effects and possess anti-inflammatory properties. Transplantation of MSCs represents as a promising therapeutic strategy to address the pathophysiologic problems of frail syndrome. Currently, MSC therapy have undergone the phase I and II trials in human subjects that have endorsed the safety and efficacy of MSCs for aging frailty. However, despite these positive results, caution is still needed with regard to potential to form tumors, and further large-scale studies are warranted to confirm the therapeutic efficacy of MSC therapy.
衰老脆弱是一种复杂的老年综合病症，随着年龄的增长变得更加普遍。由于频繁出现不良后果，它构成了一个主要的健康问题。脆弱的特点是生理内稳态的破坏和健康状况的逐渐下降。随着年龄的增长，多种因素导致脆弱的发展，包括基因组不稳定、DNA 损伤、表观遗传改变、干细胞衰竭等。这些相互关联的因素综合导致组织内稳态的丧失和脆弱性储备能力的降低。因此，衰老的机体随着器官生理功能的下降逐渐表现出脆弱的症状。值得注意的是，大脑、心血管系统、骨骼肌和内分泌系统与脆弱性密切相关。患有脆弱症的患者可能表现出器官系统储备能力的降低。由于其复杂的病理生理学，目前还没有专门的治疗方法被批准用于预防这种综合征。因此，需要采取有效的策略来干预致病过程，以改善脆弱患者的健康状况。基于细胞的治疗的最新进展极大地促进了与年龄相关的退行性疾病的改善。间充质干细胞（MSCs）可以发挥再生作用，并具有抗炎特性。MSCs 的移植被认为是一种有前途的治疗策略，可以解决脆弱综合征的病理生理问题。目前，MSC 疗法已经在人体中进行了 I 期和 II 期临床试验，这些试验证实了 MSCs 治疗衰老脆弱的安全性和有效性。然而，尽管有这些积极的结果，仍需要谨慎对待形成肿瘤的潜力，需要进一步的大规模研究来确认 MSC 疗法的治疗效果。
