MSK1 mediates BDNF-dependent MeCP2-S421 phosphorylation in postnatal striatal development and psychiatric-relevant behaviours.

Cardiorespiratory fitness (CRF) declines markedly with age, typically by 15%–25% per decade after the age of 70 yr (). Since the landmark study by Blair et al. (), CRF has consistently been confirmed as a strong, independent predictor of all-cause mortality (,), cardiovascular disease (), and loss of independence (). Moreover, the magnitude of change in CRF over time is critical for risk prediction (,). Kokkinos et al. () found that a decline of 1.0 metabolic equivalent of task (METs, 3.5 mL/kg/min) over 6 yr was associated with a 9.0% higher (HR: 1.09, 95% CI 0.99–1.19) risk of all-cause mortality in adults with moderate CRF levels. A decline of >1 METs per decade is expected with aging (). Given the strong evidence for CRF as a marker of health, maintaining a high age-specific CRF has been emphasized (). Exercise training and physical activity (PA) are key strategies for enhancing health in an aging population (). Current guidelines recommend older adults to do 150–300 min/wk of moderate-intensity aerobic PA, or 75–150 min/wk of high-intensity aerobic PA, or a combination of both (). Despite well-documented benefits, adherence remains low among older adults. In the United States () and Norway (), only 10.8% and 31.0% of older adults, respectively, meet these PA guidelines. Both moderate- and high-intensity aerobic PA improve CRF in older adults (), and randomized trials have shown superior effects of high-intensity compared with moderate-intensity aerobic exercise training on improvements in CRF (,). While the benefits of PA are well established, its role in slowing CRF decline with age remains debated. Valenzuela et al. () reported slower decline in CRF with regular PA and exercise training, whereas Hawkins et al. () found limited effects in older adults. A recent review () also questioned whether high intensity offers additional benefit over moderate intensity in improving CRF in older adults (>60 yr). Moreover, long-term effects of exercise training on CRF decline in older adults remain insufficiently examined. It is therefore of interest to better characterize the extent to which exercise training is associated with attenuated age-related decline in CRF, and to identify strategies that are associated for preserving it with increasing age. The aim of this study was to examine how different exercise intensities over a 5-yr period were associated with longitudinal changes in CRF, measured objectively as peak oxygen uptake (), in older adults. We also explored the independent associations of exercise intensity and time/week with changes in . We hypothesized that those exercising at higher intensity had a more favorable trajectory over 5 yr.