Ost 2017 Abstract MITOEAGLE Barcelona
Novel multivariate biomarkers of age-dependent sarcopenia: A blood based bioenergetics & cytokine profiling approach.
Ost M (2017)
Event: MitoEAGLE Barcelona 2017
A frequent pathophysiological phenomenon of advanced ageing in humans is sarcopenia, an age-related loss of skeletal muscle mass and strength. Physical frailty is one of the major clinical consequences of sarcopenia whereas robust biomarkers and crucial molecular mechanisms are still lacking. Mitochondrial dysfunction and circulating cytokines might have a central role in the pathophysiology of physical frailty and sarcopenia. However, the relationship between mitochondrial function, circulating cytokines and sarcopenia is unknown.
Here our goal is to evaluate novel multivariate biomarkers for sarcopenia in a blood-based bioenergetics & cytokine profiling approach. We aim to perform functional assays on mitochondrial respiratory capacity and ROS (hydrogen peroxide) production of freshly isolated human peripheral blood mononuclear cells (PBMCs) together with analyses of whole blood samples and plasma/serum for cytokine profiling from geriatric individuals aged 60-85 years (healthy age-matched controls vs. sarcopenic). Sarcopenia will be defined by using BIA predicted skeletal muscle mass and frailty status by the Fried´s criteria. The mitochondrial function of human PBMCs will be analyzed using a high-resolution respirometer (Oxygraph-2k, Oroboros Instruments). Whole blood pro-inflammatory cytokines after LPS restimulation will be measured using the Bio-Plex Multiplex system. Serum myokine values will be determined by commercial ELISA-kits. We further aim to combine the outcome of our studies on human samples with analyses on blood, PBMCs and tissue samples from physiologically aged mice (20-25 months) in comparison to young (3 months) and adult (6-10 months) mice in order to reveal molecular mechanisms.
Thereby, the results will not only provide functional information to improve the individualized diagnosis and prognosis of sarcopenic patients but will also gain new insights into the pathogenic mechanisms underlying the complexity of age-dependent sarcopenia. This might reveal novel therapeutic targets in order to design early detection, treatment, and follow-up care for sarcopenic patients.
Labels: MiParea: Respiration, Comparative MiP;environmental MiP Pathology: Aging;senescence, Other
Organism: Human, Mouse Tissue;cell: Blood cells Preparation: Intact cells
HRR: Oxygraph-2k Event: B2 PMBCs
- German Inst Human Nutrition, Dept Pharmacology/Group Energy Metab, Nuthetal, Germany