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.

Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, and immunome in whole blood, plasma, and 18 solid tissues in Rattus norvegicus over 8 weeks of endurance exercise training. The resulting data compendium encompasses 9466 assays across 19 tissues, 25 molecular platforms, and 4 training time points in young adult male and female rats. We identified thousands of shared and tissue- and sex- specific molecular alterations. Temporal multi-omic and multi-tissue analyses demonstrated distinct patterns of tissue remodeling, with widespread regulation of immune, metabolism, heat shock stress response, and mitochondrial pathways. These patterns provide biological insights into the adaptive responses to endurance training over time. For example, exercise training induced heart remodeling via altered activity of the Mef2 family of transcription factors and tyrosine kinases. Translational analyses revealed changes that are consistent with human endurance training data and negatively correlated with disease, including increased phospholipids and decreased triacylglycerols in the liver. Sex differences in training adaptation were widespread, including those in the brain, adrenal gland, lung, and adipose tissue. Integrative analyses generated novel hypotheses of disease relevance, including candidate mechanisms that link training adaptation to non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health, and tissue injury and recovery. The data and analysis results presented in this study will serve as valuable resources for the broader community and will be provided in an easily accessible public repository (https://motrpac-data.org/).

BackgroundData are sparse regarding the value of physical activity (PA) surveillance among older adults—particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study.Methods and ResultsCardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home‐based activity data were collected by hip‐worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84–0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65–0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow‐up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85–0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63–0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates.ConclusionsObjective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

Objective To evaluate the extent of variability in functional responses among participants in the LIFE study, and to identify the relative contributions of intervention adherence, physical activity, and demographic and health characteristics to this variability. Design Secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) study. Setting Multicenter U.S. institutions participating in the LIFE study. Participants A volunteer sample of 1635 sedentary men and women aged 70 to 89 years who were able to walk 400 m, but had physical limitations, defined as a score on the Short Physical Performance Battery (SPPB) of ≤9. Interventions Moderate-intensity physical activity (PA, n=818) consisting of aerobic, resistance and flexibility exercises performed both center-based (twice/wk) and in or around the home environment (3-4 times/wk) or health education (HE, n=817) consisting of weekly to monthly workshops covering relevant health information. Main Outcome Measures Physical function: gait speed over 400-m and lower extremity function (SPPB) assessed at baseline, six, twelve, and 24 months. Results Greater baseline physical function (gait speed and SPPB score) was inversely associated with Δ gait speed (regression coefficient β=−0.185, p<0.001) and ΔSPPB score (β=−0.365, p<0.001), while greater number of steps per day measured by accelerometry was positively associated with Δ gait speed (β=0.035, p<0.001) and Δ SPPB score (β=0.525, p<0.001). Other baseline factors associated with positive Δ gait speed and/or SPPB score include younger age (p<0.001), lower body mass index (p<0.001), and higher self-reported physical activity (p=0.002). Conclusions Several demographic and physical activity-related factors were associated with the extent of Δ functional outcomes among participants in the LIFE study. These factors should be considered when designing interventions for improving physical function among older adults with limited mobility.

Background Patient-reported outcomes (PROs) are clinical tools that measure patients’ goals of care and assess patient-reported physical, mental, and social well-being. Despite their value in advancing patient-centered care, routine use of PROs in stroke management has lagged. As part of the pragmatic COMPASS (Comprehensive Post-Acute Stroke Services) trial, we developed COMPASS-Care Plan (CP), a clinician-facing application that captures and analyzes PROs for stroke and transient ischemic attack patients discharged home and immediately generates individualized electronic CP. In this report, we (1) present our methods for developing and implementing COMPASS-CP PROs, (2) provide examples of CP generated from COMPASS-CP, (3) describe key functional, social, and behavioral determinants of health captured by COMPASS-CP, and (4) report on clinician experience with using COMPASS-CP in routine clinical practice for care planning and engagement of stroke and transient ischemic attack patients discharged home. Methods and Results We report on the first 871 patients enrolled in 20 North Carolina hospitals randomized to the intervention arm of COMPASS between July 2016 and February 2018; these patients completed a COMPASS follow-up visit within 14 days of hospital discharge. We also report user satisfaction results from 56 clinicians who used COMPASS-CP during these visits. COMPASS-CP identified more cognitive and depression deficits than physical deficits. Within 14-day posthospitalization, less than half of patients could list the major risk factors for stroke, 36% did not recognize blood pressure as a stroke risk factor, and 19% of patients were nonadherent with prescribed medications. Three-fourths of clinicians reported that COMPASS-CP identifies important factors impacting patients’ recovery that they otherwise may have missed, and two-thirds were highly satisfied with COMPASS-CP. Conclusions The COMPASS-CP application meets an immediate need to incorporate PROs into the clinical workflow to develop patient-centered CP for stroke patients and has high user satisfaction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02588664.