Resilience-based longevity medicine: A multiscale and dynamic integrative framework.

Abstract

Population ageing has widened the gap between lifespan and healthspan, with frailty and functional dependence increasingly shaping late-life outcomes. Yet trajectories in older age remain highly heterogeneous, suggesting that vulnerability is not determined by chronological age alone but by differences in adaptive capacity. This review reframes resilience as a dynamic, multilevel construct linking molecular maintenance, regulation within the immune-endocrine-autonomic "vital systems triad," and functional trajectories captured by the WHO Intrinsic Capacity framework. We synthesize evidence supporting operational resilience indicators based on recovery dynamics, physiological flexibility, and integrated biomarker profiles spanning multi-omics, autonomic and endocrine rhythms, digital measures, and functional performance. We further discuss how lifestyle, psychosocial, and emerging pharmacological strategies converge on shared resilience pathways and generate measurable molecular and physiological signatures. Finally, we propose an integrated longevity medicine framework as a translational model to incorporate resilience assessment into clinical decision-making, predictive modelling, and prevention-oriented policy. Positioning resilience as a modifiable target may help shift ageing strategies from disease-centred care toward preserving adaptive capacity, functional independence, and meaningful engagement across the life course.