MoTrPAC Animal Aerobic Exercise Protocol and Biorepository: A Novel Resource for Uncovering Systemic Adaptations to Aerobic Exercise and Extending Healthspan

As we age, aerobic exercise training has been shown to be one of the most effective strategies for healthspan(definition) and lifespan extension.1,2 Although aerobic exercise training is a low-cost and sustainable form of physical activity for the general population, the precise molecular and physiological pathways, which drive adaptation to exercise training have been incompletely elucidated. Despite decades of seminal findings on acute and adaptive responses to aerobic exercise training, limitations in understanding of the systemic molecular adaptive responses to aerobic exercise training somewhat limits precise tailoring of exercise training routines to optimally maximize health benefits across the population. Shenk et al.3 conducted a study within the Preclinical Animal Sites Studies of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) to delineate the molecular bases of adaptation to exercise training.4 The main goals of this study were to establish a standardized aerobic exercise protocol and to create a biospecimen repository to study temporal changes in response to the aerobic training protocol. In this study, 6-mo and 18-mo male and female Fisher 344 rats underwent an 8-week standardized progressive aerobic (5 d/wk, ∼70%–75% VO2 max) treadmill exercise training. The protocol included five experimental groups for each age: sedentary controls, 1, 2, 4, or 8 weeks of treadmill training. Eighteen solid tissues, blood, and feces were collected to establish a publicly available specimen biorepository and -omics database for future ancillary analyses to further interrogate the systemic response to aerobic exercise training. In this article, the authors compared the results on body composition, performance, and muscle physiology in the context of sex and age. The baseline anthropometric and physiologic characteristics were largely similar between the training groups and controls, despite arriving at a training facility in separate cohorts across the period of 6 months. Overall, aerobic exercise training elicited robust improvements in exercise performance. Male and female adult rats demonstrated improvements of VO2max and maximal running speed mostly at 4 and 8 weeks of training across ages accompanied by increased citric synthase activity, which reflects oxidative capacity. The authors noted sexual dimorphism and age differences in adaptive responses to the exercise training protocol. This article reports the largest effort to utilize standardized progressive aerobic exercise training in rats to study temporal adaptive response to exercise. As a strength, the consortium has selected the rat species and the training type to emulate whole-body aerobic exercise training in humans. In particular, the rat model is genetically and morphologically closer to humans than a mouse model.5 Also considering the larger organ size of rats, tissue collection is more efficient for performing multiple biological analyses with sufficient specimen. Regarding a form of aerobic exercise training used in this protocol, treadmill running engages both flexors and extensors. Also, treadmill running as opposed to wheel running or swimming can progress in a controlled manner. Additionally, the intensity used in this protocol (70%-75% of VO2max) has translatable relevance to humans as this is a recommended training intensity. The study was designed and executed in a strictly controlled manner, which assures reproducibility of future ancillary analyses. For example, the baseline characteristics were similar, and rats were trained and sampled at the same time in their dark active phase. Also, circadian rhythms and estrous cycles were considered when performing training and tissue collection to emulate human conditions. Studies to date only looked at select organs, single timepoints, sex, or age groups, which limited the understanding of the heterogeneous adaptive response to aerobic exercise. This study has had the largest cohort of rats (n = 294) involved in a progressive aerobic exercise training protocol with more than 5600 samples, including collection of 18 solid tissues, blood, and feces. This is a unique resource, which will help interrogate the systemic adaptive response to aerobic exercise and organ-to-organ communication. This study, utilizing a reliable rodent model of human aging, is the most comprehensive to date indicating the temporal changes of responses to aerobic exercise training and providing for a rich, multi-organ biorepository of solid tissues, blood, and feces. In addition to the many strengths previously mentioned, this unique resource will serve as a platform to unravel multi-organ communication in response to aerobic exercise training and made available in a rich, publicly accessible repository. Future studies leveraging this unique resource will be primed to significantly enhance our understanding of the molecular benefits of, and potentially limitations of progressive aerobic exercise. Dr Buford is a member of the MoTrPAC consortium but did not have a direct role in drafting or analysis of the referenced work of Schenk et al. None declared.