Metabolic Physiology

Metabolic Physiology

Ageing involves a gradual functional deterioration across multiple organ systems, eventually resulting in tissue dysfunction. Musculoskeletal dysfunctions are among the most common comorbidities associated with ageing, and the progressive decline in muscle mass and force (sarcopenia), and reduced muscle stem cell proliferation makes aged muscles more susceptible to damage, and slower to regenerate and recover. Consequently, most elderly people live with some combination of chronic illness, disability or frailty that negatively impacts their quality of life, restricts their ability to be socially or economically active, and dramatically increases their health care costs. In order to preserve and improve the vitality of our rapidly ageing population, there is a recognized need to identify, understand and promote various mechanisms for healthy ageing.

All established ageing hallmarks are linked to an altered metabolism, and evidence suggests that a “rewired” metabolic circuitry may either accelerate (hypercaloric diet, physical inactivity) or delay (caloric restriction, exercise) the ageing process. Nevertheless, there is a current lack of robust metabolite biomarkers to distinguish healthy from unhealthy ageing, and to assess and monitor efficacy of therapeutic interventions. Furthermore, it is unclear how covariates like sex, physical activity, or underlying comorbidities like sarcopenia or insulin resistance may determine specific metabolic signatures.

Combining different in vivo and in vitro disease models with global metabolomics profiling, we aim to comprehensively identify the range of underlying metabolic causes and consequences that distinguish healthy from unhealthy ageing. We also seek to harness this information to develop novel personalized therapeutics to mitigate unhealthy ageing trajectories, and to recover and maintain health status.