Hypoxia and Exercise in the Elderly

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. The investigators 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 the investigators will address the molecular mechanisms. In a randomized clinical study, the investigators 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.

Insulin sensitivity is assessed via the hyperinsulinemic euglycemic glucose clamp and expressed as the glucose infusion rate (GIR) in ml

Maximum oxygen uptake is measured during an incremental exhaustive exercise test and is expressed in ml/min/kg

Mitochondrial number and selected gene expression assessed from muscle biopsies from the vastus lateralis.

Fat and carbohydrate oxidation during exercise is assessed during an incremental exercise test by measurements of gas exchange and expressed as g/min

Inclusion Criteria: 55 to 75 years of age body mass index: 20 - 35 kg/m2 weight stable during last 6 months before screening (weight change < 2% body weight) HOMA-index of insulin resistance ≥ 2 to 4 units Exclusion Criteria: more than 1 hour of scheduled exercise training per week known diagnosis of type 2 diabetes or measured HbA1c > 6,5% known drug or alcohol abuse any contraindication to perform exercise training acute or chronic infections increased bleeding risk by history, INR > 1,3, use of anticoagulants

Hein M, Chobanyan-Jurgens K, Tegtbur U, Engeli S, Jordan J, Haufe S. Effect of normobaric hypoxic exercise on blood pressure in old individuals. Eur J Appl Physiol. 2021 Mar;121(3):817-825. doi: 10.1007/s00421-020-04572-6. Epub 2020 Dec 23.

Chobanyan-Jurgens K, Scheibe RJ, Potthast AB, Hein M, Smith A, Freund R, Tegtbur U, Das AM, Engeli S, Jordan J, Haufe S. Influences of Hypoxia Exercise on Whole-Body Insulin Sensitivity and Oxidative Metabolism in Older Individuals. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5238-5248. doi: 10.1210/jc.2019-00411.