Clinical Research Directory

Involvement of Muscle Mitochondrial Dysfunction in Frailty in Older Adults. Role of Exercise

This study aims to investigate the role of skeletal muscle mitochondrial dysfunction in the development of frailty in older adults and to evaluate whether a short-term, supervised resistance training intervention can improve skeletal muscle health and physical function. Frailty is a common age-related condition associated with increased vulnerability to disability, hospitalisation, and loss of independence. It is characterised by features that may include weakness, fatigue, reduced physical activity, and slower walking speed. Mitochondrial dysfunction in skeletal muscle may contribute to the development of frailty and may be further influenced by chronic conditions such as type 2 diabetes mellitus (T2DM), which are associated with metabolic alterations, inflammation, oxidative stress, and insulin resistance. Resistance training is an effective strategy to counteract age-related declines in muscle strength and physical function. However, the cellular and molecular mechanisms linking resistance training to improvements in mitochondrial function, skeletal muscle health, and resilience in older adults remain incompletely understood. The study will include approximately 120 participants comprising older adults with T2DM, healthy older adults, and young healthy controls. All participants will complete a 6-week supervised resistance training intervention, consisting of two sessions per week. Assessments performed before and after the intervention will include body composition, muscle morphology, physical performance, muscle strength, frailty, and blood-based biomarkers. Peripheral blood mononuclear cells (PBMCs) will be used to assess mitochondrial function, and plasma samples will be used for proteomic profiling. Stool samples will be collected for analysis of gut microbiota. A subset of participants will undergo skeletal muscle biopsies of the vastus lateralis at baseline and after the intervention. Muscle samples will be used to assess mitochondrial oxidative phosphorylation capacity, mitochondrial quality-control proteins, muscle fibre morphology, cell-type-specific transcriptomic profiles using single-nucleus RNA sequencing, and chromatin accessibility using ATAC-seq. The study will provide an integrated assessment of the effects of resistance training on mitochondrial function, skeletal muscle biology, physical function, frailty, circulating biomarkers, and gut microbiota. These findings may help clarify the biological mechanisms through which resistance training influences muscle health and resilience during ageing and in older adults with T2DM.

Effects of Acute Exercise in Fasting and Fed States in Individuals With Different Aerobic Fitness Levels

The aim of this study is to investigate the effects of aerobic fitness level, feeding status, and acute exercise on whole-body metabolic fuel utilization and mitochondrial function in peripheral blood mononuclear cells (PBMCs) in healthy young men. The main questions it aims to answer are: 1. Do individuals with high and low aerobic fitness levels differ in fat and carbohydrate oxidation at rest and during exercise following an overnight fast, and do their PBMC mitochondrial responses to acute exercise differ? 2. Does feeding alter fat and carbohydrate oxidation at rest and during exercise compared with the fasted state in individuals with high aerobic fitness? 3. Are PBMC mitochondrial respiration parameters and their exercise-induced changes associated with fat and carbohydrate oxidation during fasted exercise?

Independent and Combined Effects of Short-term Sulforaphane Supplementation and Exercise on Immunometabolism in Healthy Adults

The study consist of 3 interventional periods which will be completed by each consenting participant in a randomized, crossover fashion. The interventional periods will be separated by a minimum 1 week washout period. One of the interventions consists of 4 days of daily supplementation with the commercially available broccoli sprout extract capsules (BrocElite). Another intervention will consist of 4 days of daily supervised treadmill running. The exercise protocol consists of 4 minutes of high-intensity running running followed by a 3 minute recovery period, repeated for a total of 4 repetitions. The last intervention combines the above two and consists of 4 days of daily supplementation and daily supervised exercise training. Before and after each intervention, basic anthropometrics (weight, heart rate, and blood pressure) will be recorded, and a venous blood sample will be collected. Blood samples will be analyzed for metabolic and inflammatory markers. Participants will be asked to refrain from structured exercise, alcohol consumption, and broccoli consumption during each of the experimental periods. Before any testing, willing participants will provide informed consent, and fill out a few demographic, and lifestyle questionnaires. The study will be conducted at the University of British Columbia in Kelowna, BC, Canada.