Novel individualized power training protocol preserves physical function in adult and older mice

Abstract

Sarcopenia, the age-related loss of muscle mass and strength, contributes to frailty, functional decline, and reduced quality of life in older adults. Exercise is a recognized therapy for sarcopenia and muscle dysfunction, though not a cure. Muscle power declines at an increased rate compared to force, and force output declines earlier than mass. Thus, there is a need for research of exercise focusing on improving power output and functionality in older adults. Our primary purpose was proof-of-concept that a novel individualized power exercise modality would induce positive adaptations in adult mice, before the exercise program was applied to an aged cohort. We hypothesized that after following our protocol, both adult and older mice would show improved function, though there would be evidence of anabolic resistance in the older mice. Male C57BL/6 mice (12 months of age at study conclusion) were randomized into control (n = 9) and exercise (n = 6) groups. The trained group used progressive resistance (with a weighted harness) and intensity (~4-10 rpm) on a custom motorized running wheel. The mice trained similarly to a human workout regimen (4-5 sets/session, 3 sessions/week, for 12 weeks). We determined significant (p < 0.05) positive adaptations post-intervention, including: neuromuscular function (rotarod), strength/ endurance (inverted cling grip test), training physiology (force/power output per session), muscle size (soleus mass), and power/velocity of contraction (in vitro physiology). Secondly, we trained a cohort of older male mice (28 months old at conclusion): control (n = 12) and exercised (n = 8). While the older exercised mice did preserve function and gain benefits, they also demonstrated evidence of anabolic resistance.

Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise

“…To examine whether the same relationship is observed in muscles that have been subjected to WP, we first measured various structural properties of the plantaris muscle. We initially focused on the plantaris because this has been one of the most widely studied muscles in other mouse models of PRE, and as shown in Figure 3K, WP led to a modest but significant increase in its mass [17,20,34]. Our structural analyses also revealed that 13 weeks of WP did not alter the resting length of the plantaris, but it did lead to a 21% increase in the mid-belly CSA (Fig.…”

Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise

“…To examine whether the same relationship is observed in muscles that have been subjected to WP, we first measured various structural properties of the plantaris muscle. We initially focused on the plantaris because this has been one of the most widely studied muscles in other mouse models of PRE, and, as shown in Figure 3 K, WP led to a modest but significant increase in its mass [ 17 , 20 , 34 ]. Our structural analyses also revealed that 13 weeks of WP did not alter the resting length of the plantaris, but it did lead to a 21% increase in the mid-belly CSA ( Figure 4 A–C).…”

“…During the last 50 years, a variety of different animal models have been used to develop a better understanding of how PRE induces an increase in muscle mass. The majority of these models have involved the use of rodents, with earlier models largely relying on rats and more recent models relying on mice [ 15 , 16 , 17 , 18 , 19 ]. Mouse models are now viewed as being particularly advantageous because they are amenable to the wide array of genetic inventions that are often paramount to mechanistic studies.…”

Muscle memory: myonuclear accretion, maintenance, morphology, and miRNA levels with training and detraining in adult mice

“…Furthermore, myoblasts are shown to have a long-term epigenetic memory of previous exposure to stress in vitro 75 , so satellite cells could theoretically contribute to muscle memory in myofibers via recently identified fusion-independent mechanisms in vivo. 76 Future studies may employ newly developed voluntary 77 or involuntary resistance training paradigms (exercise dosage can be controlled for in the latter) 78,79 for mice that can complement PoWeR (recently reviewed here 31 ) and will aim to address how myonuclei are removed during detraining, the role of myonuclear translocation during exercise adaptation, whether epigenetic changes could explain myonuclear shape transformations with training and detraining, which exercise-induced epigenetic alterations to myonuclei are permanent, and how miR-1 could facilitate retraining adaptations.…”