Cellular senescence in bone
Open accessAbstract
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.
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Clearing senescent osteocytes increases bone strength.
“their clearance increased bone strength130”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [130]
The 'Causal role of senescent cells in mediating age-related bone loss' section reports that treatment reduced senescent osteocytes and that eliminating senescent cells improved bone strength in old mice. But the treatment eliminated senescent cells systemically and locally, not osteocytes specifically, so the paper does not establish that clearing senescent osteocytes caused the strength increase. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSenescent osteocytes with high p16 are associated with age-related bone loss in mice.
“Senescent osteocytes that express p16 at high levels have been associated with age-related bone loss in mice”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [130]
The early proinflammatory condition in regenerating tissues mimics the senescence-associated secretory phenotype (SASP); it appears beneficial if intermittent but causes pathology if chronically active.
“Not only is this condition in common for regenerating tissues in the early phase, but it also somehow mimics the senescence-associated secretory phenotype (SASP) of presenescent and senescent cells. It appears to be beneficial if intermittent, but it causes pathology if chronically active.”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [125]
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript These detection methods (summarized in Table 1) or indicators of senescence include, but are not limited to, high levels of p16Ink4a and/or p21Cip1 [2–5], senescence-associated distension of satellites (SADS; i.e., unraveled centromeres) […”
BackgroundInfluentialThe bone–fat interface: basic and clinical implications of marrow adiposity
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Cellular senescence refers to a process induced by various types of stress, including DNA damage, oncogenic mutations, reactive metabolites, mitogens, insulin-like growth factor 1 (IGF-1), telomere erosion, epigenetic stress, proteotoxic s…”
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“Given that senescent cell-to-cell variability exists [14] and the known heterogeneity of the SASP of different types of senescent cells [12, 13], it will be important in future studies to determine the efficiency by which senotherapeutics, including those that selectively eliminate senescent cells (“senolytics”) or th…”
BackgroundOld age causes de novo intracortical bone remodeling and porosity in mice
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“Whether this accumulation is due to an accelerated rate of senescent cell production with aging [26], the resistance of senescent cells to apoptosis [27], or the inability of the aged immune system to efficiently clear senescence cells [28] (or any combination thereof) is unclear.”
BackgroundAnti‐aging activity of the Ink4/Arf locus
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Telomere dysfunction in ageing and age-related diseases
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- Authors
- Farr, J. N., & Khosla, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Farr, Joshua N.
- Khosla, Sundeep
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 121
- Pages
- 121-133
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- PMC
- PMC6485943
- OpenAlex
- W2910083643
- Cited by
- 263
- References
- 113
- Citations by year
- 2026: 43 · 2025: 46 · 2024: 46 · 2023: 41 · 2022: 33 · 2021: 17 · 2020: 30 · 2019: 7
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Bone (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AG048792, P01 AG004875, R01 AR027065, K01 AR070241)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, senescence-associated secretory phenotype, bone aging, age-related bone loss, osteoporosis, senolytics, senomorphics, senotherapeutics, healthspan, bone microenvironment, tissue regeneration
- MeSH terms
- Aging, Animals, Bone and Bones, Humans, Osteocytes, Osteoporosis, Cellular Senescence
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