Hypoxia and aerobic exercise interactions in age-related metabolic muscle dysfunction.

• Applicant: Privatdozent Dr. Sven Haufe
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 261327567

Ageing is the primary risk factor for most chronic diseases including type 2 diabetes mellitus. Sarcopenia and muscular mitochondrial dysfunction with aging are crucial mechanisms leading to decreased exercise tolerance and worsened insulin sensitivity. Thus, metabolic disease and frailty, which limits physical mobility as well as quality of life, share common cellular mechanisms. Both, hypoxia and aerobic exercise regulate pathways, such as hypoxia inducible factor-1, that ameliorate age-associated metabolic muscle dysfunction. Furthermore, training under hypoxia may augment peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) activity, which regulates mitochondrial biogenesis and muscular fatty acid oxidation. We will test the hypothesis that a combination of normobaric hypoxia and exercise training elicits a synergistic effect on age-associated metabolic skeletal muscle dysfunction and we will address the molecular mechanisms. In a randomized clinical study, we will compare normoxic and hypoxic training conditions in elderly subjects. Outcome measures will focus on whole body insulin sensitivity and mitochondrial responses in skeletal muscle before and after the 8-week training intervention. We will also elucidate the molecular responses in human skeletal muscle cells to physiological hypoxia in vitro. Specifically, cells from older donors will be analyzed for the impact of electrical stimulation (mimicking exercise) under hypoxic and normoxic conditions on insulin sensitivity and mitochondrial function. Our results will offer at the same time a new physical exercise concept for elderly subjects and a molecular explanation for the beneficial effects of the normobaric hypoxia training modality. Furthermore, elucidation of underlying mechanisms will provide molecular targets for the prevention of age-associated metabolic disease and frailty.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Jürgen Eckel; Professor Dr. Armin Koch