The boundary between aging and treatable disease is collapsing — and how medicine responds to that shift will define the next era of chronic-disease prevention. A comprehensive review published in Signal Transduction and Targeted Therapy maps the current therapeutic landscape targeting the root mechanisms of biological aging, offering a synthesis of where the science actually stands versus where the hype tends to outrun the evidence.
The review organizes intervention strategies into three cellular senescence approaches — senolytics, which physically eliminate senescent cells (the dasatinib-plus-quercetin combination being the most clinically studied pairing); senomorphics, which suppress the inflammatory senescence-associated secretory phenotype without clearing cells, with rapamycin as the lead candidate; and senoreversion, an emerging category using epigenetic reprogramming to restore senescent cells to functional states. Alongside these, metabolic interventions including caloric restriction mimetics — specifically spermidine, alpha-ketoglutarate, and the antioxidant ergothioneine — show lifespan and healthspan extension in preclinical models by activating autophagy, improving mitochondrial efficiency, and reprogramming energy metabolism. The review also highlights AI-driven multiomics integration as an accelerant for identifying aging biomarkers and personalizing intervention timing.
This synthesis arrives at a pivotal moment. Individual components of this landscape — senolytics, mTOR inhibition, NAD+ precursors, epigenetic clocks — have been accumulating evidence for a decade, but the field has lacked a unified clinical framework. The review's framing around "precision longevity medicine" reflects a genuine structural shift: aging interventions are moving from one-size-fits-all to biomarker-stratified protocols. That said, critical limitations persist. Most metabolic mimetic data remain preclinical, human senolytic trials are small and short-duration, and epigenetic reprogramming in vivo carries unresolved safety signals around oncogenic risk. Target specificity remains the central translational bottleneck — no approved anti-aging therapeutic exists yet. This review is best read as a high-quality roadmap rather than a clinical mandate, confirmatory of existing mechanistic frameworks while flagging where human trial evidence is still sparse.
