Physical activity, fitness, and longevity

Longevity is a relevant cardiovascular (CV) endpoint because survival integrates incident CV disease (CVD), competing non-CVD risks, and the physiological reserve that determines resilience to aging and chronic illness. Two related constructs, physical activity (PA; a modifiable behavior) and cardiorespiratory fitness (CRF; an integrative phenotype reflecting habitual PA, genetics, cardiopulmonary function, skeletal muscle oxidative capacity, and comorbidity), are consistently associated with lower all-cause and CVD mortality across diverse populations. In this invited narrative review, we synthesize evidence linking PA and CRF to longevity, highlight the dose-response nature of benefits and the importance of activity domain and intensity, and explain why CRF generally outperforms self-reported PA for risk prediction. We address challenges in causal inference, residual confounding variables, reverse causation, and selection/measurement bias, and emphasize approaches that strengthen inference, including device-based PA assessment (e.g., accelerometry), repeated measures, and triangulation with mechanistic and trial evidence. Mechanistic pathways plausibly linking PA and CRF to survival include favorable effects on blood pressure, glycemia and insulin sensitivity, adiposity and body composition, vascular reactivity, autonomic balance, inflammation and immune function, thrombosis, and preservation of skeletal muscle and mitochondrial reserve. We review evidence in particularly relevant subgroups and discuss the "extreme exercise hypothesis", distinguishing mortality from risks, such as atrial fibrillation and accelerated coronary calcification, in endurance athletes. We conclude with practical actions for clinicians and health systems, such as prescribing activities based on the frequency, intensity, time, and type (FITT) principles, incorporating resistance training, treating CRF as a vital sign, and addressing common implementation barriers.