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Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice
by
Barve, Ruteja A
, Jagannath, Sanjana
, Risbud, Makarand V
, Ottone, Olivia K
, Akande, Esther Jesutofunmi
, Novais, Emanuel J
in
Aging
/ Animals
/ Apoptosis
/ Back pain
/ Cartilage
/ Cell cycle
/ Cell death
/ Cellular Senescence - drug effects
/ Dasatinib - pharmacology
/ Dasatinib - therapeutic use
/ Degenerative disc disease
/ Extracellular matrix
/ Genes
/ Genetic engineering
/ Heparan sulfate
/ Humans
/ Intervertebral Disc Degeneration - drug therapy
/ Intervertebral Disc Degeneration - pathology
/ Kinases
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Nucleus Pulposus - drug effects
/ Nucleus Pulposus - pathology
/ Quercetin - pharmacology
/ Quercetin - therapeutic use
/ Senescence
/ Senotherapeutics - pharmacology
/ Senotherapeutics - therapeutic use
/ Treatment Delay
2026
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Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice
by
Barve, Ruteja A
, Jagannath, Sanjana
, Risbud, Makarand V
, Ottone, Olivia K
, Akande, Esther Jesutofunmi
, Novais, Emanuel J
in
Aging
/ Animals
/ Apoptosis
/ Back pain
/ Cartilage
/ Cell cycle
/ Cell death
/ Cellular Senescence - drug effects
/ Dasatinib - pharmacology
/ Dasatinib - therapeutic use
/ Degenerative disc disease
/ Extracellular matrix
/ Genes
/ Genetic engineering
/ Heparan sulfate
/ Humans
/ Intervertebral Disc Degeneration - drug therapy
/ Intervertebral Disc Degeneration - pathology
/ Kinases
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Nucleus Pulposus - drug effects
/ Nucleus Pulposus - pathology
/ Quercetin - pharmacology
/ Quercetin - therapeutic use
/ Senescence
/ Senotherapeutics - pharmacology
/ Senotherapeutics - therapeutic use
/ Treatment Delay
2026
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Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice
by
Barve, Ruteja A
, Jagannath, Sanjana
, Risbud, Makarand V
, Ottone, Olivia K
, Akande, Esther Jesutofunmi
, Novais, Emanuel J
in
Aging
/ Animals
/ Apoptosis
/ Back pain
/ Cartilage
/ Cell cycle
/ Cell death
/ Cellular Senescence - drug effects
/ Dasatinib - pharmacology
/ Dasatinib - therapeutic use
/ Degenerative disc disease
/ Extracellular matrix
/ Genes
/ Genetic engineering
/ Heparan sulfate
/ Humans
/ Intervertebral Disc Degeneration - drug therapy
/ Intervertebral Disc Degeneration - pathology
/ Kinases
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Nucleus Pulposus - drug effects
/ Nucleus Pulposus - pathology
/ Quercetin - pharmacology
/ Quercetin - therapeutic use
/ Senescence
/ Senotherapeutics - pharmacology
/ Senotherapeutics - therapeutic use
/ Treatment Delay
2026
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Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice
Journal Article
Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice
2026
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Overview
Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis of the nucleus pulposus tissue. Transcriptomic analysis revealed tissue-specific effects of the treatment, with cell cycle regulation and JNK signaling being commonly affected across different tissue types. A comparison of SM/J data with DQ-mediated aging-dependent amelioration of disc degeneration in C57BL/6 N mice identified Junb and Zfp36l1 signaling as shared DQ targets in the mouse disc. Notably, the in vitro inhibition studies of the JUN pathway in human degenerated NP cells mimicked the benefits of DQ, namely, a reduction in senescence and SASP. This study reinforces the efficacy of senolytic treatment in ameliorating local senescence and intervertebral disc fibrosis.
Publisher
Springer Nature B.V,Nature Publishing Group
Subject
/ Animals
/ Cellular Senescence - drug effects
/ Genes
/ Humans
/ Intervertebral Disc Degeneration - drug therapy
/ Intervertebral Disc Degeneration - pathology
/ Kinases
/ Male
/ Mice
/ Nucleus Pulposus - drug effects
/ Nucleus Pulposus - pathology
/ Senotherapeutics - pharmacology
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