AbstractBackground: Irisin is a muscle derived hormone, contributing to increased fat oxidation and energy expenditure. Physical activity and exercise is known to stimulate irisin secretion. However, the potential influence of exercise mode, fitness status and age on exercise induced irisin release are less explored.Hypotheses: A single acute bout of either aerobic high-intensity interval training (HIIT) or heavy resistance training (HRT) will provide a similar increase in irisin acutely after exercise. The exercise-induced rise in irisin will be dependent on fitness level, and age, with a higher response in young vs. old individuals.Method: Twenty healthy subjects (ten young and ten old men) performed on HIIT session (4 x 4 intervals, 3 minute break) and one HRT session (10 x 4 repetition, 2-3 minute break in between) two weeks apart. Each session included, blood samples taken at baseline, 0-h, 3-h, and 24-h, and muscle biopsies at baseline, 3-h, and 24-h. Maximal oxygen uptake (V̇ O2max), one repetition maximum (1RM) and rate of force development (RFD) were assessed to determine fitness level. Irisin concentration was analyzed by enzyme-linked immunosorbent assay (ELISA) and relative gene expression of relevant gene products (FNDC5 and PGC-1α mRNA) in biopsies were determined by real-time polymerase chain reaction.Result: Blood samples from 10 young and 10 old, and muscle biopsies from 8 young and 6 old were analyzed. Circulating irisin decreased immediately after HIIT (P < 0.001), followed by an increase back to baseline at 24-h, whereas HRT had no effect. Post HIIT, FNDC5 mRNA decreased from baseline to both 3-h and 24-h (P < 0.05), and PGC-1α mRNA deceased from 3-h to 24-h (P < 0.001), while no effect were observed after HRT. The irisin response did not differ between young and old individuals, neither in blood nor muscle tissue. RFD was the only fitness parameter correlating from baseline with change in serum irisin post-HRT (positive correlation, baseline to 3-h, R = 0.522, P = 0.026).Conclusion: HIIT decreases serum irisin and muscle mRNA levels immediately after exercise, regardless of age. Contrarily, HRT does not seem to alter irisin release or transcriptions, indicating that exercise mode is a determining factor.