Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

The molecular athlete: exercise physiology from mechanisms to medals.

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial-and-error" approach, with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and interindividual differences in exercise capacity and performance, with special consideration given to aging athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise and how such adaptations translate from "molecules to medals."

Temporal dynamics of the multi-omic response to endurance exercise training.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

Exercising Immunity: Interleukin-13 Flexes Muscle.

Endurance exercise drives physiological changes in the muscle to optimize performance. In a recent study in Science, Knudsen et al. report a role for the type 2 cytokine interleukin-13 in orchestrating metabolic reprogramming that drives adaptation to endurance exercise.

The genetics of human performance.

Human physiology is likely to have been selected for endurance physical activity. However, modern humans have become largely sedentary, with physical activity becoming a leisure-time pursuit for most. Whereas inactivity is a strong risk factor for disease, regular physical activity reduces the risk of chronic disease and mortality. Although substantial epidemiological evidence supports the beneficial effects of exercise, comparatively little is known about the molecular mechanisms through which these effects operate. Genetic and genomic analyses have identified genetic variation associated with human performance and, together with recent proteomic, metabolomic and multi-omic analyses, are beginning to elucidate the molecular genetic mechanisms underlying the beneficial effects of physical activity on human health.

mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.

Survival in the wild requires organismal adaptations to the availability of nutrients. Endosomes and lysosomes are key intracellular organelles that couple nutrition and metabolic status to cellular responses, but how they detect cytosolic ATP levels is not well understood. Here, we identify an endolysosomal ATP-sensitive Na(+) channel (lysoNa(ATP)). The channel is a complex formed by two-pore channels (TPC1 and TPC2), ion channels previously thought to be gated by nicotinic acid adenine dinucleotide phosphate (NAADP), and the mammalian target of rapamycin (mTOR). The channel complex detects nutrient status, becomes constitutively open upon nutrient removal and mTOR translocation off the lysosomal membrane, and controls the lysosome's membrane potential, pH stability, and amino acid homeostasis. Mutant mice lacking lysoNa(ATP) have much reduced exercise endurance after fasting. Thus, TPCs make up an ion channel family that couples the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction.

Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress.

Exercise can alter the skeletal muscle DNA methylome, yet little is known about the role of the DNA methylation machinery in exercise capacity. Here, we show that DNMT3A expression in oxidative red muscle increases greatly following a bout of endurance exercise. Muscle-specific Dnmt3a knockout mice have reduced tolerance to endurance exercise, accompanied by reduction in oxidative capacity and mitochondrial respiration. Moreover, Dnmt3a-deficient muscle overproduces reactive oxygen species (ROS), the major contributors to muscle dysfunction. Mechanistically, we show that DNMT3A suppresses the Aldh1l1 transcription by binding to its promoter region, altering its epigenetic profile. Forced expression of ALDH1L1 elevates NADPH levels, which results in overproduction of ROS by the action of NADPH oxidase complex, ultimately resulting in mitochondrial defects in myotubes. Thus, inhibition of ALDH1L1 pathway can rescue oxidative stress and mitochondrial dysfunction from Dnmt3a deficiency in myotubes. Finally, we show that in vivo knockdown of Aldh1l1 largely rescues exercise intolerance in Dnmt3a-deficient mice. Together, we establish that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.

Meta-analysis of genomic variants in power and endurance sports to decode the impact of genomics on athletic performance and success.

Association between genomic variants and athletic performance has seen a high degree of controversy, as there is often conflicting data as far as the association of genomic variants with endurance, speed and strength is concerned. Here, findings from a thorough meta-analysis from 4228 articles exploring the association of genomic variants with athletic performance in power and endurance sports are summarized, aiming to confirm or overrule the association of genetic variants with athletic performance of all types. From the 4228 articles, only 107 were eligible for further analysis, including 37 different genes. From these, there were 21 articles for the ACE gene, 29 articles for the ACTN3 gene and 8 articles for both the ACE and ACTN3 genes, including 54,382 subjects in total, from which 11,501 were endurance and power athletes and 42,881 control subjects. These data show that there is no statistically significant association between genomic variants and athletic performance either for endurance or power sports, underlying the fact that it is highly risky and even unethical to make such genetic testing services for athletic performance available to the general public. Overall, a strict regulatory monitoring should be exercised by health and other legislative authorities to protect the public from such services from an emerging discipline that still lacks the necessary scientific evidence and subsequent regulatory approval.

Mitochondrial mutations alter endurance exercise response and determinants in mice.

Primary mitochondrial diseases (PMDs) are a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current therapeutic approaches are limited, although one approach has been exercise training. Endurance exercise is known to improve mitochondrial function in heathy subjects and reduce risk for secondary metabolic disorders such as diabetes or neurodegenerative disorders. However, in PMDs the benefit of endurance exercise is unclear, and exercise might be beneficial for some mitochondrial disorders but contraindicated in others. Here we investigate the effect of an endurance exercise regimen in mouse models for PMDs harboring distinct mitochondrial mutations. We show that while an mtDNA ND6 mutation in complex I demonstrated improvement in response to exercise, mice with a CO1 mutation affecting complex IV showed significantly fewer positive effects, and mice with an ND5 complex I mutation did not respond to exercise at all. For mice deficient in the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually worsened the dilated cardiomyopathy. Correlating the gene expression profile of skeletal muscle and heart with the physiologic exercise response identified oxidative phosphorylation, amino acid metabolism, matrisome (extracellular matrix [ECM]) structure, and cell cycle regulation as key pathways in the exercise response. This emphasizes the crucial role of mitochondria in determining the exercise capacity and exercise response. Consequently, the benefit of endurance exercise in PMDs strongly depends on the underlying mutation, although our results suggest a general beneficial effect.

DNA methylation of exercise-responsive genes differs between trained and untrained men.

BACKGROUND: Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism. RESULTS: A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites. CONCLUSIONS: Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout.

Effects of carbohydrate availability on cycling endurance at the maximal lactate steady state.

The impacts of carbohydrate (CHO) availability on time to task failure (TTF) and physiological responses to exercise at the maximal lactate steady state (MLSS) have not been studied. Ten participants (3 females, 7 males) completed this double-blinded, placebo-controlled study that involved a ramp incremental test, MLSS determination, and four TTF trials at MLSS, all performed on a cycle ergometer. With the use of a combination of nutritional (CHO, 7 g/kg, and placebo, PLA, 0 g/kg drinks) and exercise interventions [no exercise (REST) and glycogen-reducing exercise (EX)], the four conditions were expected to differ in preexercise CHO availability (RESTCHO > RESTPLA > EXCHO > EXPLA). TTF at MLSS was not improved by CHO loading, as RESTCHO (57.1 [16.6] min) and RESTPLA (57.1 [15.6] min) were not different (P = 1.00); however, TTF was ∼50% shorter in EX conditions compared with REST conditions on average (P < 0.05), with EXCHO (39.1 [9.2] min) ∼90% longer than EXPLA (20.6 [6.9] min; P < 0.001). There were effects of condition for all perceptual and cardiometabolic variables when compared at isotime (P < 0.05) and task failure (TF; P < 0.05), except for ventilation, perceptual responses, and neuromuscular function measures, which were not different at TF (P > 0.05). Blood lactate concentration was stable in all conditions for participants who completed 30 min of exercise. These findings indicate that TTF at MLSS is not enhanced by preexercise CHO supplementation, but recent intense exercise decreases TTF at MLSS even with CHO supplementation. Extreme fluctuations in diet and strenuous exercise that reduce CHO availability should be avoided before MLSS determination.NEW & NOTEWORTHY Carbohydrate (CHO) loading did not increase participants' ability to cycle at their maximal lactate steady state (MLSS); however, performing a glycogen depletion task the evening before cycling at MLSS reduced the time to task failure, even when paired with a high dose of CHO. These diet and exercise interventions influenced blood lactate concentration ([BLa]) but not the stability of [BLa]. Activities that reduce CHO availability should be avoided before MLSS determination.

Physiological assessment of a 16 day, 4385 km ultra-endurance mountain bike race: A case study.

The Tour Divide (TD) is a 4385 km ultra-endurance bicycle race that follows the continental divide from Canada to Mexico. In this case study, we performed a comprehensive molecular and physiological profile before and after the completion of the TD. Assessments were performed 35 days before the start (Pre-TD) and ∼36 h after the finish (Post-TD). Total energy expenditure was assessed during the first 9 days by doubly labelled water (2 H2 18 O), abdominal and leg tissue volumes via MRI, and graded exercise tests to quantify fitness and substrate preference. Vastus lateralis muscle biopsies were taken to measure mitochondrial function via respirometry, and vascular function was assessed using Doppler ultrasound. The 47-year-old male subject took 16 days 7 h 45 min to complete the route. He rode an average of 16.8 h/day. Neither maximal O2 uptake nor maximal power output changed pre- to post-TD. Measurement of total energy expenditure and dietary recall records suggested maintenance of energy balance, which was supported by the lack of change in body weight. The subject lost both appendicular and trunk fat mass and gained leg lean mass pre- to post-TD. Skeletal muscle mitochondrial and vascular endothelial function decreased pre- to post-TD. Overall, exercise performance was maintained despite reductions in muscle mitochondrial and vascular endothelial function post-TD, suggesting a metabolic reserve in our highly trained athlete.

Distinct adaptations of muscle endurance but not strength or hypertrophy to low-load resistance training with and without blood flow restriction.

Low-load resistance training promotes muscle strength and hypertrophic adaptations when combined with blood flow restriction (BFR). However, the effect of BFR on muscle endurance remains unclear. The aim of this study was to clarify the effects of BFR on muscle performance and adaptation, with special reference to local muscle endurance. In experiment 1, eight healthy men performed unilateral elbow flexion exercise to failure at 30% of one-repetition maximum with BFR (at 40% of estimated arterial occlusion pressure) and free blood flow (FBF). During the exercise, muscle activity and tissue oxygenation were measured from the biceps brachii. In experiment 2, another eight healthy men completed 6 weeks of elbow flexion training with BFR and FBF. The number of repetitions to failure at submaximal load (Rmax), the estimated time for peak torque output to decay by 50% during repetitive maximum voluntary contractions (half-time), one-repetition maximum, isometric strength and muscle thickness of elbow flexors were measured pre- and post-training. Blood flow restriction resulted in fewer repetitions and lower muscle tissue oxygenation at the end of exercise than FBF, while the muscle activity increased similarly to repetition failure. Blood flow restriction also resulted in a smaller post-training Rmax, which was strongly correlated with the total exercise volume over the 6 week period. Despite the smaller exercise volume, BFR resulted in similar improvements in half-time, muscle strength and thickness compared with FBF. These results suggest that the application of BFR can attenuate muscle endurance adaptations to low-load resistance training by decreasing the number of repetitions during exercise, both acutely and chronically.

Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.

Exercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes. Using this network, we formulated a logic-based ordinary differential equation model predicting time-dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP-activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross-talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Increased training load promotes sleep propensity and slow-wave sleep in endurance runners: Can a high-heat-capacity mattress topper modulate this effect?

The present study aimed to: (1) investigate sleep architecture in response to an overload training and taper periods among endurance runners; and (2) assess the sleep benefits of a high-heat-capacity mattress topper. Twenty-one trained male endurance runners performed a 2-week usual training regimen (baseline) followed by 2-week overload and taper periods. From overload to the end of the taper period, they were assigned into two groups based on the mattress topper used: high-heat-capacity mattress topper (n = 11) or low-heat-capacity mattress topper (n = 10). Training load was assessed daily using the session rating of perceived exertion. Following each period, sleep was monitored by polysomnography, and nocturnal core body temperature was recorded throughout the night. Irrespective of the group, awakening episodes > 5 min decreased following overload compared with baseline (-0.48, p = 0.05). Independently of mattress topper, each 100 A.U. increase in 7-day training load prior to polysomnographic recording was associated with higher slow-wave sleep proportion (ß = +0.13%; p = 0.05), lower sleep-onset latency (ß = -0.49 min; p = 0.05), and a reduction in the probability of transition from N1 sleep stage to wakefulness (ß = -0.12%; p = 0.05). Sleeping on a high-heat-capacity mattress topper did not affect any sleep variable compared with a low-heat-capacity mattress topper. Increased training loads promote slow-wave sleep and sleep propensity, highlighting the adaptative nature of sleep to diurnal activity and the role of sleep in physiological recovery. Further studies are required on the potential benefits of high-heat-capacity mattress toppers on sleep architecture among athletes.

Endurance exercise associated with a fructooligosaccharide diet modulates gut microbiota and increases colon absorptive area.

BACKGROUND AND AIM: Fructooligosaccharide (FOS) supplementation can stimulate beneficial intestinal bacteria growth, but little is known about its influence on training performance. Therefore, this study analyzed FOS and exercise effects on gut microbiota and intestinal morphology of C57Bl/6 mice. METHODS: Forty male mice were divided into four groups: standard diet-sedentary (SDS), standard diet-exercised (SDE), FOS supplemented (7.5% FOS)-sedentary (FDS), and FOS supplemented-exercised (FDE), n = 10 each group. Exercise training consisted of 60 min/day, 3 days/week, for 12 weeks. RESULTS: SDE and FDE groups had an increase in aerobic performance compared to the pretraining period and SDS and FDS groups (P < 0.01), respectively. Groups with FOS increased colonic crypts size (P < 0.05). The FDE group presented rich microbiota (α-diversity) compared to other groups. The FDE group also acquired a greater microbial abundance (ß-diversity) than other groups. The FDE group had a decrease in the Ruminococcaceae (P < 0.002) and an increase in Roseburia (P < 0.003), Enterorhabdus (P < 0.004) and Anaerotruncus (P < 0.006). CONCLUSIONS: These findings suggest that aerobic exercise associated with FOS supplementation modulates gut microbiota and can increase colonic crypt size without improving endurance exercise performance.

Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy.

AIM: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. METHOD: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19-38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20-40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. RESULTS: Baseline levels of gamma delta (TCRγδ+) T-cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T-cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (-11.1%, p < 0.01), despite similar ratings of perceived exertion. INTERPRETATION: Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise. WHAT THIS PAPER ADDS: TCRγδ+ T-cell baseline levels are elevated in adults with cerebral palsy (CP). The CD8+ T-cell response to exercise was blunted in adults with CP. Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP.