Chrono-Exercise Medicine: Why Biological Timing Matters for Human Health

Exercise medicine has traditionally focused on defining the optimal mode, intensity, duration, and frequency of physical activity required to improve health and performance. However, increasing evidence suggests that biological timing represents an additional and often overlooked determinant of exercise responsiveness. Circadian rhythms regulate numerous physiological processes relevant to exercise adaptation, including metabolism, mitochondrial function, protein turnover, and skeletal muscle function, while exercise itself is increasingly recognised as a potent non-photic zeitgeber capable of influencing circadian organisation. Rather than advocating a universally optimal time-of-day for exercise, this Perspective proposes "chrono-exercise medicine", as a conceptual framework through which biological timing can be integrated into personalised exercise prescription. It discusses the emerging role of circadian phenotyping, skeletal muscle molecular clocks, and temporal multi-omic approaches for understanding interindividual variability in exercise responses. Together, with key methodological, translational, and clinical challenges that must be addressed to enable biologically informed exercise prescription. It is proposed that the future of precision medicine will depend not only on how exercise is prescribed, but also on when it is prescribed and to whom.