High Intensity Interval Training in Aged Female Mice Preserves Physical, Cognitive, and Cardiovascular Function

Abstract

BACKGROUNDAlong with advancing age comes declines in physical, cognitive, and cardiovascular function. This diminished capacity may lead to decreased ability to perform activities of daily living, disability onset, and loss of independence. Exercise is a regenerative medicine therapy that can mitigate this loss of function. High intensity interval training (HIIT) is an aerobic exercise paradigm consisting of intense activity periods interspersed with bouts of active recovery. Previously we demonstrated that HIIT preserved physical function in adult, middle-aged, and older male mice. However, whether HIIT preserves physical, cognitive, and cardiovascular function, mitigates frailty, and improves brain and heart health in older adult female mice remains unknown. HYPOTHESISCognitive, physical, and cardiovascular function in older adult female C57BL/6 will be preserved in exercised mice (HIIT) versus sedentary control (SED). METHODSMice (HIIT and SED, both n=9, 24m at end) were tested pre/post-intervention for physical (rotarod, treadmill, grip meter, inverted cling, voluntary wheel running, activity monitor), cognitive (open field, novel object recognition, puzzle box, y-maze), and cardiovascular (blood pressure, echocardiogram) function, body composition, and whole body calorimetry. The mice underwent 14-weeks of HIIT training with progressive volume and intensity. RESULTSHIIT significantly (p<0.05) increased or preserved function in many tests including: aerobic capacity (+71% HIIT versus, vs, no change, NC, in SED), four limb strength/endurance (-67% SED vs -28% HIIT), forelimb strength (-16% SED vs NC HIIT), overall motor function (NC SED vs +39% HIIT), executive function (NC SED vs +73% HIIT), and exploratory behavior, which improved across multiple tests with HIIT while remaining unchanged in SED. HIIT also reduced both systolic blood pressure by 12% (-17 mmHg) and mean arterial pressure by -16 mmHg. In addition, HIIT significantly reduced cardiac fibrosis, increased muscle fiber type 2a percentage, reduced IL-1{beta} expression in the hypothalamus, and mitigated frailty onset. CONCLUSIONHIIT significantly reduced age-related functional loss in all three domains assessed while preventing frailty onset in older adult females and improving markers of brain and heart health.