A5059648760- Genetics, Aging, and Longevity in Model Organisms
- Spaceflight effects on biology
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Space Science and Extraterrestrial Life
- Circadian rhythm and melatonin
- Space Exploration and Technology
- Health, Environment, Cognitive Aging
- Exercise and Physiological Responses
- Adipose Tissue and Metabolism
- Selenium in Biological Systems
- Coenzyme Q10 studies and effects
- Nutrition and Health in Aging
- Endoplasmic Reticulum Stress and Disease
- Sports Performance and Training
- Birth, Development, and Health
- Genetics and Physical Performance
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- High Altitude and Hypoxia
- CRISPR and Genetic Engineering
- Climate Change and Health Impacts
- Cardiomyopathy and Myosin Studies
- Single-cell and spatial transcriptomics
University of Nottingham
2016-2025
Ohio University
2020-2025
Royal Derby Hospital
2014-2024
Medical Research Council
2013-2024
Versus Arthritis
2012-2024
Nottingham Biomedical Research Centre
2017-2022
National Institute for Health Research
2017-2022
Nottingham University Hospitals NHS Trust
2022
The Ohio State University
2016
University of Toledo
2016
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, single amino acid leucine (Leu) possesses most marked anabolic characteristics acting as a trigger element for initiation synthesis. While mechanisms by which Leu 'sensed' have been subject great scrutiny, branched-chain acid, can be catabolized within muscle, thus posing possibility that metabolites could involved mediating effect(s) Leu. Our...
Resistance exercise training (RET) is widely used to increase muscle mass in athletes and also aged/cachectic populations. However, the time course metabolic molecular control of hypertrophy remain poorly defined. Using newly developed deuterium oxide (D2O)-tracer techniques, we investigated relationship between long-term protein synthesis (MPS) hypertrophic responses RET. A total 10 men (23 ± 1 yr) undertook 6 wk unilateral (1-legged) RET [6 × 8 repetitions, 75% repetition maximum (1-RM)...
Key points Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET age are diminished compared younger individuals. In response 6 weeks RET, we found blunted hypertrophic underpinned by chronic deficits long‐term protein synthesis. We show this likely be result multifactorial anabolic hormones translational efficiency capacity. These results provide great insight into...
Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control mass. Traditional [ 13 C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ∼12 h, thus cannot holistically inform on diurnal MPS. This limits insight into regulation habitual metabolism in health, aging, disease while querying utility techniques predict long-term efficacy anabolic/anticatabolic interventions. We tested D 2 O...
The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of receptor, in vivo whole-body knockout models demonstrating reduced myofibre size impaired development. To understand mechanistic role upregulation VDR elicits mass/health, we studied impact over-expression (OE) before exploring importance expression upon hypertrophy humans. Wistar rats underwent electrotransfer (IVE) to overexpress...
Abstract Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans . Here, we extend work energy metabolism sex hormone signaling mice humans. We found induced changes insulin estrogen rodents Murine were most prominent liver, where observed inhibition of receptor with concomitant hepatic resistance steatosis. Based on metabolic demand, pathways mediated by vary among muscles, specifically between soleus...
Abstract Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types human body. Here, we propose that a parallel Space could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit permit advent of precision spaceflight healthcare. Alongside scientific potential, consider...
C. elegans has been established as a powerful genetic system. Use of chemically defined medium (C. Maintenance Medium (CeMM)) now allows standardization and systematic manipulation the nutrients that animals receive. Liquid cultivation automated culturing experimentation should be use in large-scale growth screening animals. We find CeMM is versatile simple. can used solid or liquid state, it stored unused for at least year, unattended actively growing cultures may maintained longer than...
SUMMARY Studies of the model organism Caenorhabditis elegans have almost exclusively utilized growth on a bacterial diet. Such culturing presents challenge to automation experimentation and introduces metabolism as secondary concern in drug environmental toxicology studies. Axenic cultivation C. can avoid these problems, yet past work suggests that axenic is unhealthy for elegans. Here we employ chemically defined liquid medium culture find development slows, fecundity declines, lifespan...
Focal adhesion kinase (FAK) is an attachment complex protein associated with the regulation of muscle mass through as-of-yet unclear mechanisms. We tested whether FAK functionally important for hypertrophy, hypothesis that knockdown (FAK-KD) would impede cell growth a trophic stimulus. C 2 12 skeletal cells harboring FAK-targeted or scrambled (SCR) shRNA were created using lentiviral transfection techniques. Both FAK-KD and SCR myotubes incubated 24 h IGF-I (10 ng/ml), additional (±IGF-1)...
Although muscle atrophy is a serious problem during spaceflight, little known about the sequence of molecular events leading to in response microgravity. We carried out spaceflight experiment using Caenorhabditis elegans onboard Japanese Experiment Module International Space Station. Worms were synchronously cultured liquid media with bacterial food for 4 days under microgravity or on 1-G centrifuge. visually observed health and movement then frozen. Upon return, we analyzed global gene...
Abstract Background The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies resistance exercise training (RET). Nonetheless, the efficacy physiological molecular impacts T therapy adjuvant short‐term RET remain poorly defined. Methods Eighteen non‐hypogonadal healthy older men, 65–75 years, were assigned a random double‐blinded fashion receive,...
Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden.C. elegans, model organism for investigating mechanisms ageing, also displays sarcopenia, but underlying mechanism(s) remain elusive.Here, we use C. elegans natural scaling lifespan in response to temperature examine relationship between mitochondrial content, function, sarcopenia.Mitochondrial content maximal ATP production rates (MAPR) display an inverse lifespan, while onset MAPR direct...
Abstract Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of concentric (CON) eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whether submaximal (60% 1RM) CON or differ their effectiveness relatively unknown. Further, the time course adaptations differs above also Therefore,...
Primary mitochondrial diseases (PMD) are amongst the most common inborn errors of metabolism causing fatal outcomes within first decade life. With marked heterogeneity in both inheritance patterns and physiological manifestations, these conditions present distinct challenges for targeted drug therapy, where effective therapeutic countermeasures remain elusive clinic. Hydrogen sulfide (H2S)-based therapeutics may offer a new option patient treatment, having been proposed as conserved...
Human space exploration poses inherent risks to astronauts' health, leading molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these bear similarities those observed during the aging process on Earth. However, our understanding of connection between shifts disease development in remains limited. Frailty...
How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, inactivation each seven genes that were down-regulated extended lifespan on ground. These encode proteins are likely related to neuronal or endocrine signaling: acetylcholine receptor, transporter, choline acetyltransferase,...
Background & aimsβ-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and an ergogenic aid exercise. Of two available forms HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased protein synthesis (MPS) reduced breakdown (MPB). The objective present study was to quantify metabolism responses...
Aims: Cells have developed quality control systems for protection against proteotoxicity. Misfolded and aggregation-prone proteins, which are behind the initiation progression of many neurodegenerative diseases (ND), known to challenge proteostasis network cells. We aimed explore role DNJ-27/ERdj5, an endoplasmic reticulum (ER)-resident thioredoxin protein required as a disulfide reductase degradation misfolded in well-established Caenorhabditis elegans models Alzheimer, Parkinson Huntington...
Abstract In this study, we report a microfluidic device for the whole-life culture of nematode Caenorhabditis elegans that allows scoring animal survival and health measures. This referred to as NemaLife chip features: (1) an optimized micropillar arena in which animals can crawl, (2) sieve channels separate progeny prevent loss adults from during maintenance, (3) ports allow rapid accessibility feeding adult-only population introducing reagents needed. The pillar geometry was accommodate...
Key points Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy. Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged. In response to VDR‐knockdown mitochondrial function and related gene‐set is impaired. vitro VDR knockdown induces myogenic dysregulation occurring impaired differentiation. These results highlight autonomous role has within mass regulation. Abstract Vitamin deficiency estimated affect ∼40%...