Cellular senescence in bone

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cellular senescence refers to a process induced by various types of stress that causes irreversible cell cycle arrest and distinct cellular alterations, including profound changes in gene expression, metabolism, and chromatin organization as well as activation/reinforcement of anti-apoptotic pathways and development of a pro-inflammatory secretome or senescence-associated secretory phenotype (SASP). However, because of challenges and technical limitations in identifying and characterizing senescent cells in living organisms, only recently have some of the diverse in vivo roles of these unique cells been discovered. New findings indicate that senescent cells and their SASP can have acute beneficial functions, such as in tissue regeneration and wound healing. However, in contrast, when senescent cells accumulate in excess chronically at sites of pathology or in old tissues they drive multiple age-associated chronic diseases. Senotherapeutics that selectively eliminate senescent cells (“senolytics”) or inhibit their detrimental SASP (“senomorphics”) have been developed and tested in aged preclinical models. These studies have established that targeting senescence is a powerful anti-aging strategy to improve “healthspan” – i.e., the healthy period of life free of chronic disease. The roles of senescence in mediating age-related bone loss have been a recent focus of rigorous investigation. Studies in mice and humans demonstrate that with aging, at least a subset of most cell types in the bone microenvironment become senescent and develop a heterogeneous SASP. Furthermore, age-related bone loss can be alleviated in old mice, with apparent advantages over anti-resorptive therapy, by reducing the senescent cell burden genetically or pharmacologically with the first class of senolytics or a senomorphic. Collectively, these findings point to targeting senescence as a transformational strategy to extend healthspan, therefore providing strong rationale for identifying and optimizing senotherapeutics to alleviate multiple chronic diseases of aging, including osteoporosis, and set the stage for translating senotherapeutics to humans, with clinical trials currently ongoing.

Original languageEnglish (US)
Pages (from-to)121-133
Number of pages13
JournalBone
Volume121
DOIs
StatePublished - Apr 1 2019

Fingerprint

Cell Aging
Bone and Bones
Osteoporosis
Phenotype
Chronic Disease
Cell Cycle Checkpoints
Wound Healing
Chromatin
Regeneration
Clinical Trials
Pathology
Gene Expression

Keywords

  • Aging
  • Bone
  • Disease prevention
  • Osteocyte
  • Osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Cellular senescence in bone. / Farr, Joshua; Khosla, Sundeep.

In: Bone, Vol. 121, 01.04.2019, p. 121-133.

Research output: Contribution to journalArticle

Farr, Joshua ; Khosla, Sundeep. / Cellular senescence in bone. In: Bone. 2019 ; Vol. 121. pp. 121-133.
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