Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential.
Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential.
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DOI：
10.3389/fcell.2021.793088
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发表时间：
2021
影响因子：
5.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
He Y;Xie W;Li H;Jin H;Zhang Y;Li Y
衰老促进了大多数哺乳动物的退行性病理，其特征是分子、细胞、组织和器官水平上的功能进行性下降，并占发展中国家和发达国家的大量医疗保健支出。骨质疏松症是肌肉骨骼系统中一种显著的增龄性疾病。骨质疏松症被定义为渐进性和广泛性的慢性骨骼肌疾病，包括肌肉质量、力量和功能的加速丧失，这与不良功能结果的增加有关，进化性地指伴随着其他老年综合征的肌肉萎缩。人们已经做出了更多的努力来阐明石棺减少的机制，新的发现表明，通过调节细胞衰老等基本机制来延缓与年龄相关的石棺减少可能是可行的。细胞衰老是指随着生物年龄的增长，主要受p53/p21CIP1和p16INK4a/pRb通路调控的基本不可逆的生长停滞，可能通过肌肉干细胞(MuSCs)功能障碍和衰老相关的分泌表型(SASP)而导致骨骼减少，而细胞衰老在抗癌进展、组织再生和伤口愈合方面可能具有有益的功能。到目前为止，在小鼠和人类身上进行的各种研究已经确定，靶向细胞衰老是缓解石棺减少症的有效策略。然而，衰老细胞促进骨质疏松症进展的机制还需要进一步研究。我们综述了肌肉干细胞(MuSCs)功能障碍和由细胞衰老引起的SASP的可能机制，它们与骨质疏松症的关系，目前出现的与骨质疏松症相关的靶向细胞衰老的治疗机会，以及从遗传学或药理学上开发临床干预的潜在途径。
Aging promotes most degenerative pathologies in mammals, which are characterized by progressive decline of function at molecular, cellular, tissue, and organismal levels and account for a host of health care expenditures in both developing and developed nations. Sarcopenia is a prominent age-related disorder in musculoskeletal system. Defined as gradual and generalized chronic skeletal muscle disorder, sarcopenia involves accelerated loss of muscle mass, strength and function, which is associated with increased adverse functional outcomes and evolutionally refers to muscle wasting accompanied by other geriatric syndromes. More efforts have been made to clarify mechanisms underlying sarcopenia and new findings suggest that it may be feasible to delay age-related sarcopenia by modulating fundamental mechanisms such as cellular senescence. Cellular senescence refers to the essentially irreversible growth arrest mainly regulated by p53/p21CIP1 and p16INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP) while cellular senescence may have beneficial functions in counteracting cancer progression, tissue regeneration and wound healing. By now diverse studies in mice and humans have established that targeting cellular senescence is a powerful strategy to alleviating sarcopenia. However, the mechanisms through which senescent cells contribute to sarcopenia progression need to be further researched. We review the possible mechanisms involved in muscle stem cells (MuSCs) dysfunction and the SASP resulting from cellular senescence, their associations with sarcopenia, current emerging therapeutic opportunities based on targeting cellular senescence relevant to sarcopenia, and potential paths to developing clinical interventions genetically or pharmacologically.
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DOI：
10.1111/apha.12532
发表时间：
2016-01
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Brook MS;Wilkinson DJ;Phillips BE;Perez-Schindler J;Philp A;Smith K;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
5.2
作者：
Alcalde-Estevez, Elena;Asenjo-Bueno, Ana;Lopez-Ongil, Susana
通讯作者：
Lopez-Ongil, Susana
DOI：
10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1038/nrrheum.2017.60
发表时间：
2017-06
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Dennison EM;Sayer AA;Cooper C
通讯作者：
Cooper C