High intensity interval training improves physical performance in aged female mice: A comparison of mouse frailty assessment tools.

Frailty syndrome increases the risk for disability and mortality, and is a major health concern amidst the geriatric shift in the population. High intensity interval training (HIIT), which couples bursts of vigorous activity interspersed with active recovery intervals, shows promise for the treatment of frailty. Here we compare and contrast five Fried physical phenotype and one deficit accumulation based mouse frailty assessment tools for identifying the impacts of HIIT on frailty and predicting functional capacity, underlying pathology, and survival in aged female mice. Our data reveal a 10-minute HIIT regimen administered 3-days-a-week for 8-weeks increased treadmill endurance, gait speed and maintained grip strength. One frailty tool identified a benefit of HIIT for frailty, but many were trending suggesting HIIT was beneficial for physical performance in these mice, but the 8-week timeframe may have been insufficient to induce frailty benefits. Finally, most frailty tools distinguished between surviving or non-surviving mice, whereas half correlated with functional capacity measured by nest building ability, and none correlated with underlying pathology. In summary, this study supports the ongoing development of mouse assessment tools as useful instruments for frailty research.

Short Session High Intensity Interval Training and Treadmill Assessment in Aged Mice.

High intensity interval training (HIIT) is emerging as a therapeutic approach to prevent, delay, or ameliorate frailty. In particular short session HIIT, with regimens less than or equal to 10 min is of particular interest as several human studies feature routines as short as a few minutes a couple times a week. However, there is a paucity of animal studies that model the impacts of short session HIIT. Here, we describe a methodology for an individually tailored and progressive short session HIIT regimen of 10 min given 3 days a week for aged mice using an inclined treadmill. Our methodology also includes protocols for treadmill assessment. Mice are initially acclimatized to the treadmill and then given baseline flat and uphill treadmill assessments. Exercise sessions begin with a 3 min warm-up, then three intervals of 1 min at a fast pace, followed by 1 min at an active recovery pace. Following these intervals, the mice are given a final segment that starts at the fast pace and accelerates for 1 min. The HIIT protocol is individually tailored as the speed and intensity for each mouse are determined based upon initial anaerobic assessment scores. Additionally, we detail the conditions for increasing or decreasing the intensity for individual mice depending on performance. Finally, intensity is increased for all mice every two weeks. We previously reported in this protocol enhanced physical performance in aged male mice and here show it also increases treadmill performance in aged female mice. Advantages of our protocol include low administration time (about 15 min per 6 mice, 3 days a week), strategy for individualizing for mice to better model prescribed exercise, and a modular design that allows for the addition or removal of the number and length of intervals to titrate exercise benefits.

High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice.

Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks. Baseline and end point assessments included body composition, physical performance, and frailty based on criteria from the Fried physical frailty scale. HIIT-trained mice demonstrated dramatic improvement in grip strength (HIIT 10.9% vs -3.9% in sedentary mice), treadmill endurance (32.6% vs -2.0%), and gait speed (107.0% vs 39.0%). Muscles from HIIT mice also exhibited greater mass, larger fiber size, and an increase in mitochondrial biomass. Furthermore, HIIT exercise led to a dramatic reduction in frailty scores in five of six mice that were frail or prefrail at baseline, with four ultimately becoming nonfrail. The uphill treadmill HIIT exercise sessions were well tolerated by aged mice and led to performance gains, improvement in underlying muscle physiology, and reduction in frailty.