Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training

Abstract

Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms of lipid peroxidation levels and muscle quality.

Efficacy of Age-Specific High-Intensity Stretch-Shortening Contractions in Reversing Dynapenia, Sarcopenia, and Loss of Skeletal Muscle Quality

“…It should be mentioned at the fundamental level that these skeletal muscle contractions typically have been investigated using isolated preparations; although there are limitations to the physiological translation of these types of models and investigations, they have produced a wealth of essential data [63][64][65]. In addition, there are groups, including ours, that implement skeletal muscle contractions in a model that is more physiologically relevant in that it combines all types of skeletal muscle contractions as they are conducted and utilized in vivo: this scenario is known as either SSCs [12,13,[66][67][68] or a subcategory of the SSCs defined as the stretch-shortening cycle [11,[69][70][71][72]. The nuance and distinction between these two independently combined contraction paradigms is that as the SSCs include and incorporate the sequential pre-activation of the isometric contraction followed by successive lengthening and shortening contractions, and these SSCs are incurred during all activities of daily movement in mammals [50].…”

“…It is chronic resistance exercise loading, or training, that is unique in promoting restoration or improvements in skeletal muscle performance (i.e., strength, work capacity, fatigue resistance, etc.) and skeletal muscle mass [83,84], as evidence for these findings exist in both human [57,71,83] and animal studies [66]; yet, little evidence exists for improving skeletal muscle quality in various populations, including aged populations [7,59]. There are numerous human studies that have suggested that resistance exercise training is beneficial in countering distinct components of musculoskeletal health and aging [71,83,84]; however, no translational study has shown that resistance exercise training can restore musculoskeletal health with aging to youthful states entirely.…”

“…For these reasons and with these limitations in mind, fundamental, in vivo animal models that are valid and representative of the human exposure-response relationship with respect to aging and exercise are an essential tool for investigating and quantifying these phenomena due to the exquisite control they allow over the biomechanical loading exposure as well as providing a means to evaluate, characterize, and quantify the integrated skeletal muscle response systematically. Interestingly, only recently have investigations begun to question and quantify the impact age-specific RTET imparts on skeletal muscle quality and whether this specific and sensitive outcome metric (i.e., "biomarker") is modifiable with aging [13,38,66,86]. Initial studies by Cutlip and colleagues provided a basis for investigating non-injurious SSC RTET exposure in a validated, fundamental rodent model of aging, which quantified the adaptive and maladaptive response in young and old skeletal muscle, respectively [13].…”

“…These reports provided evidence that a general SSC RTET employed 3 days per week over a 1-month period repeatedly resulted in skeletal muscle performance decrements with no improvements in skeletal muscle quality in old rodents (i.e., 30 months of age). More recently, Rader and colleagues have conducted follow-up work that extended from those initial findings and have reported that when SSC RTET was implemented in old rodents that included both the 3 days per week RTET group and compared this with a 2 days per week RTET group over a 1-month period, the old rodents that underwent 2 days per week RTET adapted and were indistinguishable from their younger counterparts and, notably, had their skeletal muscle quality restored to that of a youthful state [66]. In a subsequent investigation from this same group, both the mode (i.e., isometric contractions alone, utilized as a minimalistic RTET approach) as well as repetition number was studied.…”

“…for all outcomes predicted, particularly in aged populations. Also, these studies emphasize that there is a very narrow "window" involving both the specificity and sensitivity of these physical/mechanical loading variables with respect to an RTET exposure-response relationship with aging, and that particularly frequency of exposure, rather than mode or repetition number, may be the more precise variable for consideration when designing and implementing age-specific RTET in aged populations [66,85] when skeletal muscle performance, skeletal muscle mass, and skeletal muscle quality are the focal outcomes for positively affecting, and restoring, health-span. Thus, when considered in total, the fundamental evidence from SSC RTET suggests that the utility of this mode of exercise is efficacious and applicable for translational approaches in aging populations.…”