Targeting Cell Senescence for the Treatment of Age-Related Bone Loss

• Published in: Current osteoporosis reports Vol. 17; no. 2; pp. 70 - 85
• Main Authors: Pignolo, Robert J., Samsonraj, Rebekah M., Law, Susan F., Wang, Haitao, Chandra, Abhishek
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2019
• Subjects: Epidemiology; Medicine; Medicine & Public Health; Orthopedics; Section Editors; Therapeutics and Medical Management (S Jan de Beur and B Clarke; Topical Collection on Therapeutics and Medical Management; Telomere dysfunction; Aging; Osteoporosis; Cell senescence; Senescence-associated secretory phenotype; Senolytic drug
• ISSN: 1544-1873; 1544-2241
• DOI: 10.1007/s11914-019-00504-2

Purpose of Review
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.
Recent Findings
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.
Summary
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.