Exercise

Two fundamental types of physical activity can be distinguished, endurance exercise and strength exercise, although there is a continuum between these exercise modalities. ^[1] Repeated, episodic bouts of skeletal muscle contraction undertaken as structured exercise training are a potent stimulus for physiological adaptation in many organs, remodeling muscle size, force, endurance, and contractile velocity. ^[2]

Adaptation to exercise training is underpinned by the activation or repression of molecular pathways in response to each acute session, transducing neuronal, mechanical, metabolic, and hormonal signals into changes in transcription, translation, and protein turnover. ^[2] AMP-activated protein kinase (AMPK) is a master energy-state sensor that, when activated by exercise, promotes glucose and fatty acid utilization and mediates beneficial adaptations including mitochondrial biogenesis and angiogenesis across many tissues. ^[3] Exercise exerts a powerful action on metabolism, and depending on its intensity and duration different mechanisms are recruited to make energy available under coordinated hormonal control. ^[1]

International consensus guidelines position structured exercise as medicine, showing a dose-response effect that can be individualised through different modalities, volumes and intensities according to the health state or medical condition. ^[4] Global consensus recommendations state that physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, and reduce premature mortality, with progressive resistance training singled out as indispensable for maintaining functional capacity in older adults. ^[5] Evidence from systematic reviews and meta-analyses supports beneficial effects of exercise training on cognitive and brain health in both cognitively unimpaired and impaired older individuals, though the effects are often modest and depend on training parameters. ^[6] Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, and exercise has emerged as a key intervention for reducing the risk of age-related cognitive decline and dementia. ^[7]

Cardiorespiratory fitness, measured by VO2max, is a strong and independent predictor of all-cause and disease-specific mortality and a key factor in promoting life expectancy. ^[8] Physical activity and exercise influence the cellular and molecular drivers of biological aging, slowing aging rates, a foundational aspect of geroscience, so that sub-optimal levels correlate with increased disease prevalence in aging populations. ^[5] Because exercise can substitute for pharmacological treatment in conditions such as depression and serve as a primary intervention where no effective drug exists, it contributes to deprescribing potentially inappropriate medications in older adults. ^[4]