Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Curr Osteoporos Rep. 2019 Apr;17(2):70-85. doi: 10.1007/s11914-019-00504-2.
We review cell senescence in the context of age-related bone loss by broadly discussing aging mechanisms in bone, currently known inducers and markers of senescence, the senescence-associated secretory phenotype (SASP), and the emerging roles of senescence in bone homeostasis and pathology.
Cellular senescence is a state of irreversible cell cycle arrest induced by insults or stressors including telomere attrition, oxidative stress, DNA damage, oncogene activation, and other intrinsic or extrinsic triggers and there is mounting evidence for the role of senescence in aging bone. Cellular aging also instigates a SASP that exerts detrimental paracrine and likely systemic effects. With aging, multiple cell types in the bone microenvironment become senescent, with osteocytes and myeloid cells as primary contributors to the SASP. Targeting undesired senescent cells may be a favorable strategy to promote bone anabolic and anti-resorptive functions in aging bone, with the possibility of improving bone quality and function with normal aging and/or disease.
本文广泛讨论了骨骼衰老的机制、目前已知的衰老诱导剂和标志物、衰老相关分泌表型 (SASP) ，以及衰老在骨骼稳态和病理中的新兴作用，以此来探讨细胞衰老与年龄相关性骨丢失的关系。
细胞衰老，又称衰老细胞，是一种由端粒磨损、氧化应激、DNA 损伤、癌基因激活和其他内在或外在触发因素等损伤或应激诱导的不可逆细胞周期停滞状态，越来越多的证据表明衰老在衰老骨骼中起作用。衰老细胞还会引发 SASP，从而产生有害的旁分泌作用，可能还有全身作用。随着年龄的增长，骨骼微环境中的多种细胞类型都会衰老，成骨细胞和骨髓细胞是 SASP 的主要贡献者。针对不需要的衰老细胞可能是一种促进衰老骨骼中骨合成和抗吸收功能的有利策略，有可能改善正常衰老和/或疾病过程中的骨骼质量和功能。
