Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

Background: Disorders of gastric function are highly prevalent, but diagnosis often remains symptom-based and inconclusive. Body surface gastric mapping is an emerging diagnostic solution, but current approaches lack scalability and are cumbersome and clinically impractical. We present a novel scalable system for non-invasively mapping gastric electrophysiology in high-resolution (HR) at the body surface. Methods:The system comprises a custom-designed stretchable high-resolution "peel-and-stick" sensor array (8 × 8 pre-gelled Ag/AgCl electrodes at 2 cm spacing; area 225 cm 2 ), wearable data logger with custom electronics incorporating bioamplifier chips, accelerometer and Bluetooth synchronized in real-time to an App with cloud connectivity. Automated algorithms filter and extract HR biomarkers including propagation (phase) mapping. The system was tested in a cohort of 24 healthy subjects to define reliability and characterize features of normal gastric activity (30 m fasting, standardized meal, and 4 h postprandial).Key Results: Gastric mapping was successfully achieved non-invasively in all cases (16 male; 8 female; aged 20-73 years; BMI 24.2 ± 3.5). In all subjects, gastric electrophysiology and meal responses were successfully captured and quantified non-invasively (mean frequency 2.9 ± 0.3 cycles per minute; peak amplitude at mean 60 m postprandially with return to baseline in <4 h). Spatiotemporal mapping showed regular and consistent wave activity of mean direction 182.7° ± 73 (74.7% antegrade, 7.8% retrograde, 17.5% indeterminate). Conclusions and Inferences:BSGM is a new diagnostic tool for assessing gastric function that is scalable and ready for clinical applications, offering several biomarkers that are improved or new to gastroenterology practice.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.