4.5 Article

The role of senolytics in osteoporosis and other skeletal pathologies

Journal

MECHANISMS OF AGEING AND DEVELOPMENT
Volume 199, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2021.111565

Keywords

Osteoporosis; Cellular senescence; Osteocytes; Age-related bone loss

Funding

  1. NIH [P01 AG062413, R21 AG065868, R01 AG063707, R01 DK128552]

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The skeletal system undergoes irreversible structural deterioration with aging, leading to increased fracture risk and detrimental changes in mobility, posture, and gait. Clearance of senescent cells may improve bone mass and microarchitecture, preventing age-related bone loss.
The skeletal system undergoes irreversible structural deterioration with aging, leading to increased fracture risk and detrimental changes in mobility, posture, and gait. This state of low bone mass and microarchitectural changes, diagnosed as osteoporosis, affects millions of individuals worldwide and has high clinical and economic burdens. Recently, pre-clinical studies have linked the onset of age-related bone loss with an accumulation of senescent cells in the bone microenvironment. These senescent cells appear to be causal to age-related bone loss, as targeted clearance of these cells leads to improved bone mass and microarchitecture in old mice. Additionally, other pathologies leading to bone loss that result from DNA damage, such as cancer treatments, have shown improvements after clearance of senescent cells. The development of new therapies that clear senescent cells, termed senolytics, is currently underway and may allow for the modulation of bone loss that results from states of high senescent cell burden, such as aging.

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