Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model
- PMID: 39865135
- DOI: 10.1007/s11357-025-01520-0
Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model
Abstract
Inflammaging, a state of chronic low-grade inflammation associated with aging, has been linked to the development and progression of various disorders. Cellular senescence, a state of irreversible growth arrest, is another characteristic of aging that contributes to the pathogenesis of cardiovascular pathology. Senescent cells accumulate in tissues over time and secrete many inflammatory mediators, further exacerbating the inflammatory environment. This senescence-associated secretory phenotype can promote tissue dysfunction and remodeling, ultimately leading to the development of age-related cardiovascular pathologies, such as mitral valve myxomatous degeneration. The species-specific form of canine myxomatous mitral valve disease (MMVD) provides a unique opportunity to investigate the early causes of induction of ECM remodeling in mitral valve leaflets in the human form of MMVD. Studies have shown that in both humans and dogs, the microenvironment of the altered leaflets is inflammatory. More recently, the focus has been on the mechanisms leading to the transformation of resting VICs (qVICs) to myofibroblast-like VICs (aVICs). Cells affected by stress fall into a state of cell cycle arrest and become senescent cells. aVICs, under the influence of TGF-β signaling pathways and the mTOR complex, enhance ECM alteration and accumulation of systemic inflammation. This review aims to create a fresh new view of the complex interaction between aging, inflammation, immunosenescence, and MMVD in a canine model, as the domestic dog is a promising model of human aging and age-related diseases.
Keywords: DNA damage response; Immunosenescence; Inflammaging; MMVD; Mitochondria; Myxomatous mitral valve disease; Telomere.
© 2025. The Author(s), under exclusive licence to American Aging Association.
Conflict of interest statement
Declarations. Conflict of interest: The authors declare no competing interests.
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