Senomorphic agents: Multi-target strategies to tame the senescence-associated secretory phenotype for healthy ageing.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and therapeutic concepts without original human data
PubMed 42498087 · doi:10.1016/j.exger.2026.113249
What was done
This narrative review summarizes mechanisms and translational potential of senomorphic agents, which suppress the senescence-associated secretory phenotype (SASP) without eliminating senescent cells. The authors evaluate pathways including NF-κB, mTOR, JAK/STAT, and cGAS-STING, and classify agents into repurposed metabolic modulators (e.g., metformin), natural products (e.g., urolithin A), and targeted synthetic inhibitors (e.g., ruxolitinib) across contexts such as neurodegenerative diseases, cardiovascular ageing, and osteoarthritis.
What was found
The abstract reports no quantitative results, sample sizes, or numerical effect sizes. It qualitatively describes senomorphic pathways, therapeutic strategies, synergistic combination potential with senolytics, and current translational hurdles.
Why it matters
Targeting the senescent secretome rather than clearing senescent cells offers an alternative therapeutic paradigm that may preserve non-pathological physiological cell functions. This paper categorizes current multi-target pharmacological approaches and highlights key obstacles to clinical application.
Limits
This is a narrative review presenting no new primary empirical data or meta-analytic synthesis. The abstract identifies substantial translational barriers, including a lack of specific senescence biomarkers, absence of targeted tissue delivery systems, and a lack of long-term safety data in humans.
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