Osteocyte Cellular Senescence
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OSTEOCYTES (J DELGADO-CALLE AND J KLEIN-NULEND, SECTION EDITORS)
Osteocyte Cellular Senescence Joshua N. Farr 1,2,3
&
Japneet Kaur 1,2 & Madison L. Doolittle 1,2 & Sundeep Khosla 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Senescent cells are now known to accumulate in multiple tissues with aging and through their inflammation (the senescence-associated secretory phenotype, SASP) contribute to aging and chronic diseases. Here, we review the roles of senescent osteocytes in the context of bone loss. Recent Findings Numerous studies have established that senescent osteocytes accumulate in the bone microenvironment with aging in mice and in humans. Moreover, at least in mice, elimination of senescent cells results in attenuation of age-related bone loss. Osteocyte senescence also occurs in response to other cellular stressors, including radiotherapy, chemotherapy, and metabolic dysfunction, where it appears to mediate skeletal deterioration. Summary Osteocyte senescence is linked to bone loss associated with aging and other conditions. Senescent osteocytes are potential therapeutic targets to alleviate skeletal dysfunction. Additional studies better defining the underlying mechanisms as well as translating these exciting findings from mouse models to humans are needed. Keywords Osteocyte . Senescence . Aging . Radiotherapy . Chemotherapy . Type 2 diabetes mellitus
Introduction Cellular senescence is a cell fate, like differentiation, proliferation, or apoptosis, that involves essentially irreversible proliferative arrest, tumor suppressor activation, altered chromatin organization, and apoptosis resistance and frequently is associated with increased protein synthesis [1]. The phenomenon was discovered in the early 1960s [2] by Leonard This article is part of the Topical Collection on Osteocytes * Joshua N. Farr [email protected] Japneet Kaur [email protected] Madison L. Doolittle [email protected] Sundeep Khosla [email protected] 1
Division of Endocrinology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
2
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
3
Division of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Hayflick who found that with prolonged serial culture, normal human embryonic fibroblasts eventually lost their capacity to divide, yet they remained viable. This growth arrest phase was coined “senescence” [2]. It is now well established that various types of stress converge to cause a cell to enter the cellular senescence program. Examples of senescence-inducing stressors include internal and external cell damaging insults such as DNA breaks, oncogenic stimuli, reactive metabolites and oxygen species, proteotoxic stress, and inflammation [1]. The pathways that drive a cell into senescence are largely centered on the cyclin-dependent kinase inhibitors, most notably p16Ink
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