PreprintCited by 57Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsMesenchymal stem cell research

Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton

Open access
Doolittle, Madison L., Saul, Dominik, Kaur, Japneet, Rowsey, Jennifer L., Vos, Stephanie J., Pavelko, Kevin D., Farr, Joshua N., Monroe, David G. +1 more·2023·Nature Communications

Preprint — 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.01.12.523760

Cites

134 of 134 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Venue
Nature Communications
Publisher
openRxiv
Published
2023-01-13
Volume
14
Issue
1
Pages
4587-4587
ISSN
2041-1723 (ISSN-L)
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review