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Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
by
Rowsey, Jennifer L.
, Pavelko, Kevin D.
, Saul, Dominik
, Monroe, David G.
, Doolittle, Madison L.
, Vos, Stephanie J.
, Farr, Joshua N.
, Kaur, Japneet
, Khosla, Sundeep
in
38
/ 38/91
/ 631/443/63
/ 631/443/7
/ 631/80/509
/ 64/60
/ 82/58
/ Aging
/ Aging - genetics
/ Animals
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Biomarkers
/ Cellular Senescence - genetics
/ Cytometry
/ DNA damage
/ Galactosidase
/ Humanities and Social Sciences
/ In vivo methods and tests
/ Mesenchyme
/ Mice
/ multidisciplinary
/ Multiple criterion
/ Osteoblasts
/ Osteocytes
/ Osteogenesis
/ Phenotypes
/ Phenotyping
/ Science
/ Science (multidisciplinary)
/ Senescence
/ Senotherapeutics
/ Skeleton
/ β-Galactosidase
2023
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Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
by
Rowsey, Jennifer L.
, Pavelko, Kevin D.
, Saul, Dominik
, Monroe, David G.
, Doolittle, Madison L.
, Vos, Stephanie J.
, Farr, Joshua N.
, Kaur, Japneet
, Khosla, Sundeep
in
38
/ 38/91
/ 631/443/63
/ 631/443/7
/ 631/80/509
/ 64/60
/ 82/58
/ Aging
/ Aging - genetics
/ Animals
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Biomarkers
/ Cellular Senescence - genetics
/ Cytometry
/ DNA damage
/ Galactosidase
/ Humanities and Social Sciences
/ In vivo methods and tests
/ Mesenchyme
/ Mice
/ multidisciplinary
/ Multiple criterion
/ Osteoblasts
/ Osteocytes
/ Osteogenesis
/ Phenotypes
/ Phenotyping
/ Science
/ Science (multidisciplinary)
/ Senescence
/ Senotherapeutics
/ Skeleton
/ β-Galactosidase
2023
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Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
by
Rowsey, Jennifer L.
, Pavelko, Kevin D.
, Saul, Dominik
, Monroe, David G.
, Doolittle, Madison L.
, Vos, Stephanie J.
, Farr, Joshua N.
, Kaur, Japneet
, Khosla, Sundeep
in
38
/ 38/91
/ 631/443/63
/ 631/443/7
/ 631/80/509
/ 64/60
/ 82/58
/ Aging
/ Aging - genetics
/ Animals
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Biomarkers
/ Cellular Senescence - genetics
/ Cytometry
/ DNA damage
/ Galactosidase
/ Humanities and Social Sciences
/ In vivo methods and tests
/ Mesenchyme
/ Mice
/ multidisciplinary
/ Multiple criterion
/ Osteoblasts
/ Osteocytes
/ Osteogenesis
/ Phenotypes
/ Phenotyping
/ Science
/ Science (multidisciplinary)
/ Senescence
/ Senotherapeutics
/ Skeleton
/ β-Galactosidase
2023
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Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
Journal Article
Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton
2023
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Overview
Senescence drives organismal aging, yet the deep characterization of senescent cells in vivo remains incomplete. Here, we apply mass cytometry by time-of-flight using carefully validated antibodies to analyze senescent cells at single-cell resolution. We use multiple criteria to identify senescent mesenchymal cells that are growth-arrested and resistant to apoptosis. These p16 + Ki67-BCL-2+ cells are highly enriched for senescence-associated secretory phenotype and DNA damage markers, are strongly associated with age, and their percentages are increased in late osteoblasts/osteocytes and CD24
high
osteolineage cells. Moreover, both late osteoblasts/osteocytes and CD24
high
osteolineage cells are robustly cleared by genetic and pharmacologic senolytic therapies in aged mice. Following isolation, CD24+ skeletal cells exhibit growth arrest, senescence-associated β-galactosidase positivity, and impaired osteogenesis in vitro. These studies thus provide an approach using multiplexed protein profiling to define senescent mesenchymal cells in vivo and identify specific skeletal cell populations cleared by senolytics.
Technical challenges have previously hindered the detailed study of in vivo senescent cells. Here, the authors deeply characterize senescent skeletal cells across murine aging, establishing CD24 as a marker of osteolineage cells cleared by senolytics.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/91
/ 64/60
/ 82/58
/ Aging
/ Animals
/ Cellular Senescence - genetics
/ Humanities and Social Sciences
/ Mice
/ Science
/ Skeleton
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