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

Robert Pignolo, Rebekah M. Samsonraj, Susan F. Law, Haitao Wang, Abhishek Chandra

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)70-85
Number of pages16
JournalCurrent Osteoporosis Reports
Volume17
Issue number2
DOIs
StatePublished - Apr 15 2019

Fingerprint

Cell Aging
Osteoporosis
Bone and Bones
Phenotype
Osteocytes
Telomere
Myeloid Cells
Cell Cycle Checkpoints
Oncogenes
DNA Damage
Oxidative Stress
Homeostasis
Pathology

Keywords

  • Aging
  • Cell senescence
  • Osteoporosis
  • Senescence-associated secretory phenotype
  • Senolytic drug
  • Telomere dysfunction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Targeting Cell Senescence for the Treatment of Age-Related Bone Loss. / Pignolo, Robert; Samsonraj, Rebekah M.; Law, Susan F.; Wang, Haitao; Chandra, Abhishek.

In: Current Osteoporosis Reports, Vol. 17, No. 2, 15.04.2019, p. 70-85.

Research output: Contribution to journalReview article

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AU - Samsonraj, Rebekah M.

AU - Law, Susan F.

AU - Wang, Haitao

AU - Chandra, Abhishek

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N2 - 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.

AB - 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.

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