Bone cell senescence: mechanisms and perspectives.

Abstract

Age-related bone loss is in large part the consequence of senescence mechanisms that impact bone cell number and function. In recent years, progress has been made in the understanding of the molecular mechanisms underlying bone cell senescence that contributes to the alteration of skeletal integrity during aging. These mechanisms can be classified as intrinsic senescence processes, alterations in endogenous anabolic factors, and changes in local support. Intrinsic senescence mechanisms cause cellular dysfunctions that are not tissue specific and include telomere shortening, accumulation of oxidative damage, impaired DNA repair, and altered epigenetic mechanisms regulating gene transcription. Aging mechanisms that are more relevant to the bone microenvironment include alterations in the expression and signaling of local growth factors and altered intercellular communications. This review provides an integrated overview of the current concepts and interacting mechanisms underlying bone cell senescence during aging and how they could be targeted to reduce the negative impact of senescence in the aging skeleton.