ArticleThe Journal of clinical investigation2023
Local senolysis in aged mice only partially replicates the benefits of systemic senolysis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
- Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.Nature medicine · 2024Trial
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Future directions of osteoanabolic therapies in osteoporosis: Integrating current anabolic agents and emerging senescence-targeted strategies.Best practice & research. Clinical rheumatology · 2026Review
- Article
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- Aged murine bone marrow myeloid and mesenchymal cells develop unique senescence phenotypes.The Journal of clinical investigation · 2026Article
- Inflammatory cytokines secreted from senescent periodontal ligament cells influence the osteocyte network in alveolar bone.JBMR plus · 2026Article
- Immune-metabolic convergence in skeletal remodeling disorders: shared osteoimmune, senescent and lipid mechanisms across aging-related and immune-mediated bone disease.Frontiers in immunology · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1-34 Administration and Bone Loss.Aging cell · 2026Article
- Osteoimmune senescence in aging-related bone diseases.Frontiers in immunology · 2026Review
- Article
- The triangular drivers of bone aging: mechanistic insights and therapeutic targets in cellular senescence, estrogen deficiency, and gut microenvironment dysregulation.Frontiers in cell and developmental biology · 2026Review
- Endothelial senescent-cell-specific clearance alleviates metabolic dysfunction in obese mice.Cell metabolism · 2025Article
- Biomaterials targeting senescent cells for bone regeneration: State-of-the-art and future perspectives.Bioactive materials · 2025Review
- Senolytic Treatment Improves Responsiveness to Mechanical Loading in the Skeleton of Aged Mice.International journal of molecular sciences · 2025Article
- Musculoskeletal biomarkers in health and disease: implications for the aging spine-a review for spinal surgeons by the SRS adult spinal deformity task force on senescence.Spine deformity · 2025Review
- Pyrroloquinoline Quinone Is an Effective Senomorphic Agent to Target the Pro-Inflammatory Phenotype of Senescent Cells.Aging cell · 2025Article
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Clearance of senescent cells (SnCs) can prevent several age-related pathologies, including bone loss. However, the local versus systemic roles of SnCs in mediating tissue dysfunction remain unclear. Thus, we developed a mouse model (p16-LOX-ATTAC) that allowed for inducible SnC elimination (senolysis) in a cell-specific manner and compared the effects of local versus systemic senolysis during aging using bone as a prototype tissue. Specific removal of Sn osteocytes prevented age-related bone loss at the spine, but not the femur, by improving bone formation without affecting osteoclasts or marrow adipocytes. By contrast, systemic senolysis prevented bone loss at the spine and femur and not only improved bone formation, but also reduced osteoclast and marrow adipocyte numbers. Transplantation of SnCs into the peritoneal cavity of young mice caused bone loss and also induced senescence in distant host osteocytes. Collectively, our findings provide proof-of-concept evidence that local senolysis has health benefits in the context of aging, but, importantly, that local senolysis only partially replicates the benefits of systemic senolysis. Furthermore, we establish that SnCs, through their senescence-associated secretory phenotype (SASP), lead to senescence in distant cells. Therefore, our study indicates that optimizing senolytic drugs may require systemic instead of local SnC targeting to extend healthy aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.