Anti-infective drugs display diverse, class-specific effects on vascular aging, with macrolides and tetracyclines exerting anti-ageing effects while aminoglycosides and fluoroquinolones accelerate vascular ageing.
Systematic Review (n=92)
Do anti-infective drugs modulate vascular ageing mechanisms in in vitro, animal, and human models?
Anti-infective drugs display diverse, class-specific effects on vascular aging, highlighting the need to consider these mechanisms for safer prescribing and potential drug repurposing.
Background: Vascular aging is a major driver of cardiovascular, metabolic, and degenerative diseases, characterized by oxidative stress, mitochondrial dysfunction, endothelial senescence, and impaired proteostasis. Emerging data show that anti-infective drugs can influence these aging pathways beyond antimicrobial activity. However, their capacity to accelerate or slow vascular ageing has not been clearly defined. This review summarizes current evidence on how anti-infective agents modulate vascular ageing mechanisms. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Studies from 2000 to 2024 were searched in major indexed databases. Eligible studies included in vitro, animal, and human research evaluating the effects of anti-infective agents on endothelial function, vascular senescence markers (p16INK4a, p21, SA-β-gal), oxidative stress, mitochondrial activity, inflammation, or proteostasis, key determinants of vascular ageing. Studies lacking mechanistic aging endpoints were excluded. Extracted data included drug class, model type, study design, and age-related outcomes. Risk of bias was assessed using SYRCLE, RoB-2, ROBINS-I, and narrative appraisal for in vitro studies. Results: Ninety-eight studies were identified; after removing six duplicates, ninety-two met the criteria. Macrolides, tetracyclines, and selected antivirals exerted anti-ageing effects by suppressing senescence-associated secretory phenotype (SASP), preserving mitochondrial integrity, reducing oxidative stress, and enhancing autophagy. Aminoglycosides and fluoroquinolones accelerated vascular ageing by generating reactive oxygen species, inducing DNA damage, and disrupting proteostasis. Antiviral protease inhibitors worsened endothelial dysfunction and metabolic aging. Antifungals such as itraconazole and amphotericin B impaired mitochondrial activity and angiogenesis, contributing to ageing phenotypes. Antiparasitic drugs showed mixed aging outcomes: chloroquine promoted autophagy and longevity, whereas thiabendazole impaired vascular stability. Broad-spectrum antibiotics disrupted the gut-vascular axis, increasing trimethylamine N-oxide, a mediator of inflammatory vascular aging. Discussion: Anti-infective drugs display diverse, class-specific effects on vascular aging. Recognizing these age-related actions is essential for safer prescribing and for repurposing anti-infective agents to target pathological vascular aging mechanisms.
Silumbwe et al. (Wed,) conducted a systematic review in Vascular ageing (n=92). Anti-infective drugs was evaluated on Modulation of vascular ageing mechanisms. Anti-infective drugs display diverse, class-specific effects on vascular aging, with macrolides and tetracyclines exerting anti-ageing effects while aminoglycosides and fluoroquinolones accelerate vascular ageing.