BBSRC MIBTP - Stopping the ROS: Linking metabolism and anti-oxidant supplementation to reduce oxidative stress in exercise and ageing

Background: The recent introduction of metabolomics [1] in to biological research has highlighted the importance of metabolites in many biological processes. Changes in metabolism can be observed over short (diurnal) [2] and long-time periods (decades) [3], between genders [3] and during exercise regimes [4]. Metabolites are involved in many processes from metabolism through to signalling and regulation of biological processes. One major biological process observed to increase during exercise (especially intensive exercise) and as humans age is oxidative stress. Interestingly, one lifestyle intervention to improve healthy ageing is exercise. Molecular changes during intensive exercise include the production of radicals and other reactive oxygen species (ROS) in active skeletal muscle (and other tissues). This in turn leads to long-lasting muscle damage (2-5 days), which inhibits a muscles’ capacity to generate force. This reduction in muscle capacity adds to the observed decline in muscle function with ageing. Numerous studies have examined the potential positive effect of dietary supplementation on markers of muscle damage and oxidative stress [5] but, thus far, findings have been inconclusive. Research has provided some evidence that fruit-derived polyphenolic compounds (e.g. present in fruit juices) have the potential to improve recovery following strenuous exercise. Less is known about its effect in the endurance exercise setting, such as cycling or running and the effects of supplementation within a healthy population in relation to healthy ageing.
Aims: We will study the interaction between age, exercise, dietary interventions, oxidative stress and metabolism and their combined influence on recovery following exercise and in relation to ageing in active individuals
Areas of investigation:
(1) Exercise studies in human participants. Biofluids and muscle tissue will be collected in multiple human studies of high intensity interval training (HIIT) and endurance training (ET) in different age groups and in the presence and absence of polyphenol-rich fruit juice interventions (Aldred).
(2) Study of global and tissue-specific markers of oxidative stress in relation to (1). The impact of age, exercise type (HIIT vs ET) and polyphenol-rich fruit juices on markers of oxidative stress and muscle damage will be determined. These will include Single Cell Gel Electrophoresis assay (’comet assay’) to assess DNA damage, serum creatine kinase, markers of protein and lipid oxidation, total antioxidant status and inflammatory markers (e.g. IL-6) (Aldred).
(3) Study of metabolism in relation to (1). Targeted and non-targeted metabolomic studies (applying liquid chromatography-mass spectrometry) will be performed to identify metabolic changes related to exercise type, influence of age on exercise recovery and polyphenol-rich fruit juice interventions (Dunn).
(4) In-vitro and ex-vivo validation of in-vivo studies in muscle cells/tissues. Biological discoveries from 1-3 will be validated and further studied (including further biochemical interventions) in-vitro to determine the molecular and biochemical mechanisms related to oxidative stress and associated metabolic changes, using a range of high resolution technologies (Lavery).