Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton
Open accessPreprint — published as 10.1038/s41467-023-40393-9 · Paper page
Abstract
Senescence drives organismal aging, yet the deep characterization of senescent cells in vivo remains incomplete. Here, we applied mass cytometry by time-of-flight (CyTOF) using carefully validated antibodies to analyze senescent cells at single-cell resolution. We used multiple criteria to identify senescent mesenchymal cells that were growth arrested and resistant to apoptosis (p16+/Ki67-/BCL-2+; “p16KB” cells). These cells were highly enriched for senescence-associated secretory phenotype (SASP) and DNA damage markers and were strongly associated with age. p16KB cell percentages were also increased in CD24+ osteolineage cells, which exhibited an inflammatory SASP in aged mice and were robustly cleared by both genetic and pharmacologic senolytic therapies. Following isolation, CD24+ skeletal cells exhibited growth arrest, SA-βgal positivity, and impaired osteogenesis in vitro . These studies thus provide a new approach using multiplexed protein profiling by CyTOF to define senescent mesenchymal cells in vivo and identify a highly inflammatory, senescent CD24+ osteolineage population cleared by senolytics.
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The Senotherapeutic Effects of APPA (Apocynin [AP] and Paeonol [PA]) on Senescent Human Chondrocytes
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- Authors
- Doolittle, M. L., Saul, D., Kaur, J., Rowsey, J. L., Vos, S. J., Pavelko, K. D., Farr, J. N., Monroe, D. G., & Khosla, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Khosla, Sundeep
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2023-01-13
- Volume
- 14
- Issue
- 1
- Pages
- 4587-4587
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10390564
- OpenAlex
- W4385426207
- Cited by
- 57
- References
- 134
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 21 · 2023: 4
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health and Human Services (T32AG049672, R01 AG076515, P01AG062413, R01 AG063707, U54AG079754, R01 DK128552)
- Mayo Clinic (UL1TR002377)
- American Federation for Aging Research
- Glenn Foundation for Medical Research
- Deutsche Forschungsgemeinschaft (413501650)
- Fondation pour la Recherche Médicale
- National Institutes of Health (AG062413, UL1TR002377)
- Center for Clinical and Translational Science, Mayo Clinic (UL1 TR 002377)
- National Institute on Aging (R01AG063707, T32AG049672, U54AG079754, P01AG062413, R01AG076515)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128552)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cellular senescence, senolytic therapy, senescent cells, bone aging, osteoblasts, osteocytes, senescence-associated secretory phenotype, p16, Ki-67, Bcl-2, mass cytometry, bone formation, growth arrest, DNA damage, senolytics
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