Abstract
Overexpression of p62 in muscle inhibits aging-induced muscle-derived CXCL13 production and muscle fibrosis
Physiology (Bethesda, Md.), Vol.41(S1), 2301312
05/2026
DOI: 10.1152/physiol.2026.41.S1.2301312
Abstract
Abstract only Aging has been demonstrated to induce low-grade systemic inflammation and fibrosis by increasing the level of inflammatory cytokines and chemokines, which play key roles in the development of organ dysfunction and increased disease risk. Skeletal muscle is a pivotal organ in the production of cytokines and chemokines and is strongly affected by aging. However, the molecular mechanisms regulating the production of cytokines and chemokines, as well as fibrosis, in skeletal muscle are not fully understood. In this study, we observed that aging resulted in spleen enlargement, a hallmark of systemic inflammation, and skeletal muscle fibrosis in mice. These were mitigated in muscle-specific sequestosome 1/p62 (p62) overexpression (p62 mTg) mice, and tended to be exacerbated in muscle-specific p62 deficient (p62 skmKO) mice. Aging led to elevated serum and muscle levels of C-X-C motif chemokine ligand 13 (CXCL13); however, these increases were inhibited in p62 mTg mice. Aging activated SRY-box transcription factor 4 (Sox4 - a transcription factor for CXCL13) in muscle, and this was also suppressed in p62 mTg mice. Upstream, Sox4 and CXCL13 proteins can be driven by transforming growth factor β1 (TGF-β1) in cultured myotubes, which was found to be increased in aging skeletal muscle along with increased expression of thrombospondin 1/THBS1 (THBS1) protein. Importantly, these age-related increases in TGF-β and THBS1 expression were also mitigated in p62 mTg mice. Collectively, these findings point to skeletal muscle p62 as a potential therapeutic target for age-related systemic inflammation and muscle fibrosis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Details
- Title: Subtitle
- Overexpression of p62 in muscle inhibits aging-induced muscle-derived CXCL13 production and muscle fibrosis
- Creators
- Mami Yamada - Nagoya City UniversityEiji Warabi - University of TsukubaHisashi Oishi - Nagoya City UniversityVitor A Lira - University of IowaMitsuharu Okutsu - Nagoya City University
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.41(S1), 2301312
- DOI
- 10.1152/physiol.2026.41.S1.2301312
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Publisher
- AMER PHYSIOLOGICAL SOC
- Language
- English
- Date published
- 05/2026
- Academic Unit
- Dental Research; Health, Sport, and Human Physiology
- Record Identifier
- 9985164081602771
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