Beyond the 900-day rule: Reclaiming healthspan as geroscience’s primary goal

Abstract

The recently proposed “900-day rule” in mouse aging studies—requiring lifespan extension over ultra-long-lived controls—aims to identify interventions that modulate intrinsic aging. While this standard raises scientific rigor, it may reduce relevance to how most organisms, including humans, actually age. In reality, aging unfolds under metabolically and immunologically stressful conditions—not in sterile, genetically uniform environments. Most people experience chronic inflammation, metabolic drift, and functional decline long before death. Prioritizing only pristine models risks overlooking the hallmarks of manifest aging: frailty, cognitive loss, immune erosion. This Viewpoint argues for a dual-track strategy: rigorous lifespan testing in ideal models should be complemented by phenotype-driven studies in real-world aging models—such as conventionally housed mice in academic settings—that reflect typical aging trajectories. Interventions like GlyNAC, NLRP3 inhibition, and CaAKG demonstrate broad functional benefits in real-world aging models—effects that may be dismissed as “noise” but are likely the most translationally meaningful. In the case of CaAKG, substantial reductions in frailty occurred even when lifespan gains were modest—highlighting the decoupling of healthspan from longevity. By embracing both intrinsic and manifest aging, geroscience can better target what matters most: improving healthspan for the many—not just lifespan for the few.