Pharmacological targeting of the senescence-associated secretory phenotype in atherosclerosis: therapeutic potential of senolytics and senomorphics.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analysis
PubMed 42133066 · doi:10.1007/s00210-026-05416-4
What was done
This narrative review synthesized literature on the role of cellular senescence and the senescence-associated secretory phenotype (SASP) in atherosclerosis, focusing on the mechanisms, preclinical efficacy, and translational potential of senolytic and senomorphic drug candidates.
What was found
The abstract reports no numerical findings or statistical measures. Preclinical evidence indicates that senolytics (such as dasatinib plus quercetin, fisetin, and lanatoside C) clear senescent cells via anti-apoptotic pathways (BCL-2, PI3K/AKT, HSP90), resulting in decreased plaque area, restricted necrotic core expansion, and improved plaque stability. Senomorphics (such as rapamycin, metformin, and JAK/STAT or NF-κB inhibitors) suppress SASP cytokine and matrix metalloproteinase secretion through mTOR, NF-κB, and JAK/STAT pathways.
Why it matters
Targeting cellular senescence offers a theoretical approach to address residual vascular inflammation in atherosclerotic cardiovascular disease beyond standard lipid-lowering therapy.
Limits
The paper is a non-systematic review providing no original empirical data. Reported efficacy is limited to preclinical animal models, and clinical utility is currently unverified with unresolved concerns regarding dosing, drug-drug interactions, patient selection, and long-term safety.
Cited by
- supports mTOR-dampening drugs suppress secretion in senescent cells rather than killing them, and the suppression lasts beyond drug application because it breaks a pro-inflammatory feedback loop that takes time to re-establish.