Senolytic treatment for low back pain

Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory and degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, <i>o</i>-vanillin and RG-7112, remove SnCs in human intervertebral discs (IVDs) and reduce SASP release, but it is unknown whether they can treat LBP. <i>sparc<sup>-/-</sup></i> mice, with LBP, were treated orally with <i>o</i>-vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration scores in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. Together, our data suggest RG-7112 and <i>o</i>-vanillin as potential disease-modifying drugs for LBP and other painful disorders linked to cell senescence.

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Publication Details

Journal
Science Advances
Published
2025-03-14
DOI
https://doi.org/10.1126/sciadv.adr1719
Citations
17
Primary Topic
Plant Toxicity and Pharmacological Properties
Type
article
Field-Weighted Citation Impact
13.70
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article

Senolytic treatment for low back pain

Lisbet Haglund, A. Gilbert, Saber Ghazizadeh Darband, Hosni Cherif et al.
17 citations
Science Advances
Plant Toxicity and Pharmacological Properties
13.70
article

Senolytic treatment for low back pain

Lisbet Haglund, A. Gilbert, Saber Ghazizadeh Darband, Hosni Cherif, Reza Sharif‐Naeini, Matthew Mannarino, Laura S. Stone, Magali Millecamps, Jean Ouellet, Cédric Peirs, Elsa Cousineau, Seunghwan Lee, Chan Gao, Kai Sheng, Oliver Wu Martinez
article en
17 citations

Abstract

Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory and degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, <i>o</i>-vanillin and RG-7112, remove SnCs in human intervertebral discs (IVDs) and reduce SASP release, but it is unknown whether they can treat LBP. <i>sparc<sup>-/-</sup></i> mice, with LBP, were treated orally with <i>o</i>-vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration scores in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. Together, our data suggest RG-7112 and <i>o</i>-vanillin as potential disease-modifying drugs for LBP and other painful disorders linked to cell senescence.

Science AdvancesVol. 11(11)
University of Minnesota (US), Inserm (FR), McGill University Health Centre (CA), Shriners Hospitals for Children - Canada (CA), University of Clermont Auvergne (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Clermont Université (FR), McGill University (CA)
Good health and well-being
Openalex Percentile: Top 1%
Plant Toxicity and Pharmacological Properties
13.70
DOIOpen Access PDFOpenAlex
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