Abstract
Context With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the "Geroscience Hypothesis," which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss. Methods This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence," "aging," and "bone." Results There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice. Conclusions Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1282-1290 |
| Number of pages | 9 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 103 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2018 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
Cite this
Inhibiting Cellular Senescence : A New Therapeutic Paradigm for Age-Related Osteoporosis. / Khosla, Sundeep; Farr, Joshua; Kirkland, James L.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 4, 01.04.2018, p. 1282-1290.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibiting Cellular Senescence
T2 - A New Therapeutic Paradigm for Age-Related Osteoporosis
AU - Khosla, Sundeep
AU - Farr, Joshua
AU - Kirkland, James L
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Context With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the "Geroscience Hypothesis," which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss. Methods This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence," "aging," and "bone." Results There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice. Conclusions Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.
AB - Context With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the "Geroscience Hypothesis," which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss. Methods This summary is based on the authors' knowledge of the field supplemented by a PubMed search using the terms "senescence," "aging," and "bone." Results There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice. Conclusions Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.
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UR - http://www.scopus.com/inward/citedby.url?scp=85045432585&partnerID=8YFLogxK
U2 - 10.1210/jc.2017-02694
DO - 10.1210/jc.2017-02694
M3 - Article
C2 - 29425296
AN - SCOPUS:85045432585
VL - 103
SP - 1282
EP - 1290
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -