Exercise training which meets the recommendations set by the National Physical Activity Guidelines ensues a multitude of health benefits towards the prevention and treatment of various chronic diseases. However, not all individuals respond well to exercise training. That is, some individuals have no response, while others respond poorly. Genetic background is known to contribute to the inter-individual (human) and -strain (e.g., mice, rats) variation with acute exercise and exercise training, though to date, no specific genetic factors have been identified that explain the differential responses to exercise. In this review, we provide an overview of studies in human and animal models that have shown a significant contribution of genetics in acute exercise and exercise training-induced adaptations with standardized endurance and resistance training regimens, and further describe the genetic approaches which have been used to demonstrate such responses. Finally, our current understanding of the role of genetics and exercise is limited primarily to the nuclear genome, while only a limited focus has been given to a potential role of the mitochondrial genome and its interactions with the nuclear genome to predict the exercise training-induced phenotype(s) responses. We therefore discuss the mitochondrial genome and literature that suggests it may play a significant role, particularly through interactions with the nuclear genome, in the inherent ability to respond to exercise.

Physical inactivity contributes to cardiovascular disease, type II diabetes, obesity, and some types of cancer. While the literature is clear that there is genetic regulation of physical activity with existing gene knockout data suggesting that skeletal muscle mechanisms contribute to the regulation of activity, actual differences in end-protein expression between high- and low-active mice have not been investigated. This study used two-dimensional differential gel electrophoresis coupled with mass spectrometry to evaluate the proteomic differences between high-active (C57L/J) and low-active (C3H/HeJ) mice in the soleus and extensor digitorum longus (EDL). Furthermore, vivo-morpholinos were used to transiently knockdown candidate proteins to confirm their involvement in physical activity regulation. Proteins with higher expression patterns generally fell into the calcium-regulating and Krebs (TCA) cycle pathways in the high-active mice (e.g., annexin A6, P = 0.0031; calsequestrin 1; P = 0.000025), while the overexpressed proteins in the low-active mice generally fell into cytoskeletal structure- and electron transport chain-related pathways (e.g., ATPase, P = 0.031; NADH dehydrogenase, P = 0.027). Transient knockdown of annexin A6 and calsequestrin 1 protein of high-active mice with vivo-morpholinos resulted in decreased physical activity levels (P = 0.001). These data suggest that high- and low-active mice have unique protein expression patterns and that each pattern contributes to the peripheral capability to be either high- or low-active, suggesting that different specific mechanisms regulate activity leading to the high- or low-activity status of the animal.

Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels.Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity.Results: 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p < 0.0001; female: p < 0.0001) and had significantly higher body fat (male: p < 0.0001; female: p < 0.0001). The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male (p = 0.05, 70 ± 28%) and female mice (p = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat.Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones.

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Respiratory infectious diseases resulting from bacterial or viral pathogens such as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial virus (RSV), or influenza, are major global public health concerns. Lower respiratory tract infections are leading causes of morbidity and mortality, only behind ischemic heart disease and stroke (GBD 2015 LRI Collaborators in Lancet Infect Dis 17(11):1133–1161, 2017). Developing countries are particularly impacted by these diseases. However, while many are infected with viruses such as RSV (> 90% of all individuals are infected by age 2), only sub-populations develop severe disease. Many factors may contribute to the inter-individual variation in response to respiratory infections, including gender, age, socioeconomic status, nutrition, and genetic background. Association studies with functional single nucleotide polymorphisms in biologically plausible gene candidates have been performed in human populations to provide insight to the molecular genetic contribution to pulmonary infections and disease severity. In vitro cell models and genome-wide association studies in animal models of genetic susceptibility to respiratory infections have also identified novel candidate susceptibility genes, some of which have also been found to contribute to disease susceptibility in human populations. Genetic background may also contribute to differential efficacy of vaccines against respiratory infections. Development of new genetic mouse models such as the collaborative cross and diversity outbred mice should provide additional insight to the mechanisms of genetic susceptibility to respiratory infections. Continued investigation of susceptibility factors should provide insight to novel strategies to prevent and treat disease that contributes to global morbidity and mortality attributed to respiratory infections.

Nanomaterials are a relatively new class of materials that acquire novel properties based on their reduced size. While these materials have widespread use in consumer products and industrial applications, the potential health risks associated with exposure to them remain to be fully characterized. Carbon nanotubes are among the most widely used nanomaterials and have high potential for human exposure by inhalation. These nanomaterials are known to penetrate the cell membrane and interact with intracellular molecules, resulting in a multitude of documented effects, including oxidative stress, genotoxicity, impaired metabolism, and apoptosis. While the capacity for carbon nanotubes to damage nuclear DNA has been established, the effect of exposure on mitochondrial DNA (mtDNA) is relatively unexplored. In this study, we investigated the potential of multi-walled carbon nanotubes (MWCNTs) to impair mitochondrial gene expression and function in human bronchial epithelial cells (BECs). Primary BECs were exposed to subcytotoxic doses (up to 3 μg/ml) of MWCNTs for 5 days and assessed for changes in expression of all mitochondrial protein-coding genes, heteroplasmies, and insertion/deletion mutations (indels). Exposed cells were also measured for cytotoxicity, metabolic function, mitochondrial abundance, and mitophagy. We found that MWCNTs upregulated mitochondrial gene expression, while significantly decreasing oxygen consumption rate and mitochondrial abundance. Confocal microscopy revealed induction of mitophagy by 2 hours of exposure. Mitochondrial DNA heteroplasmy and insertion/deletion mutations were not significantly affected by any treatment. We conclude that carbon nanotubes cause mitochondrial dysfunction that leads to mitophagy in exposed BECs via a mechanism unrelated to its reported genotoxicity.

Objectives: The primary aim was to determine the level of physiological stress evoked while playing music in a standing position as indicated by heart rate (HR) response. A secondary aim was to analyze the effect of music genre (classic rock, western, contemporary Christian, and metal rock) on the relative HR response. Lastly, we considered potential physiological initiators of the music-playing-induced HR response. Methods: HR response was monitored in 27 professional musicians (3 women, 24 men) between the ages of 21and 67 yrs old during rehearsal and public performances. The percent maximal HR (%MHR) evoked was determined by taking a percentage of the age-predicted maximal HR for each musician and comparing the average %MHR in each genre during public and rehearsal events. The role of the potential initiators of these responses (e.g., number of years playing in public, event type, instrument type, tempo, etc.) was determined using multiple regression analyses. Results: The overall average %MHR responses were 52±5% and 59±5% during rehearsal and public performances, respectively, with genre type having a significant effect on the HR response (p=0.01). Body mass index and tempo were each found to be significant contributors to the HR response while playing music (r2=0.506, p=0.001). Conclusion: Playing music professionally evokes considerable increases in HR response, with music genre influencing the level of the physiological response. We concluded that 50% of the HR response while playing music was associated with body mass index, music tempo, and instrument type.