Translational Geroscience Strategies for Delaying Multimorbidity

The global rise in aging populations emphasizes an urgency to mitigate the escalating burden of chronic age-related diseases. This review discusses advances in geroscience to reframe aging as a modifiable risk factor rather than an inevitability. It explores emerging interventions that hold promise to delay or prevent multiple age-related pathologies concurrently by targeting conserved biological drivers of aging, genomic instability, epigenetic dysregulation, mitochondrial dysfunction, and stem cell exhaustion. Innovations in senolytics and epigenetic reprogramming exemplify transformative strategies to shift the medical paradigm from treating individual diseases to extending healthspan. Critical challenges in translation are addressed, including inconsistent intervention efficacy across species, safety concerns in cellular reprogramming, and ethical debates over prioritizing life versus health span. The review highlights sex-specific disparities in therapeutic outcomes and encourages precision-based approaches to ensure equitable benefits. This review further details a multidimensional roadmap to compress morbidity and redefine healthy aging by leveraging complex tools such as artificial intelligence-driven drug discovery, organ-on-a-chip models, and multiomics integration. It calls for stronger integration of mechanistic discoveries into clinical practice to promote a paradigm of aging balanced on resilience and vitality rather than decline.