Age-related circadian disruptions accelerate physiological decline and shorten lifespan. Enhancing circadian amplitude has emerged as a promising strategy for ameliorating age-associated disorders. Here, we show that the circadian-phase-optimized administration of 3'-deoxyadenosine (3dA) strengthens circadian amplitude in hypothalamic paraventricular nucleus (PVN) neurons, mitigates aging biomarkers, and extends mouse lifespan. 3dA restores clock synchrony and hormonal rhythms, including cortico...