Nemec 2017 Abstract MITOEAGLE Barcelona
Functional state of mitochondria in patients with preclinical cognitive deficit.
Event: MitoEAGLE Barcelona 2017
Sedentary ageing increases the risk of neurodegenerative and metabolic diseases [1,2,3]. Within an initial pre-intervention part of our 3-months supervised aerobic/strength exercise intervention study, we examined the whole body and muscle metabolic characteristics in 34 seniors with subjective or mild cognitive impairment.
Glucose metabolism was examined by oGTT, insulin sensitivity by euglycemic hyperinsulinemic clamp; Resting Energy Expenditure (REE), metabolic substrate preference (RQ) and flexibility (ΔRQ) by indirect calorimetry (Ergostik, Geratherm Respiratory). Cognitive functions were assessed with a battery of validated cognitive tests (MMSE, CogState, Memtrax), and muscle energy metabolism by O2k high-resolution respirometry (Oroboros ) and 31P-Magnetic Resonance Spectroscopy (Magnetom, Siemens). Functional muscle and aerobic fitness parameters included (i) maximum voluntary contraction force, (ii) rate of force development, (iii) Berg balance test, (iv) VO2max by Rockport walking test. Biopsy of m. vastus lateralis was performed in local anesthesia using Bergström needle technique. SUIT protocols RP1 and RP2  were used to evaluate oxygen consumption rate (pmol s-1mg-1 tissue wet weight) in saponin permabilized muscle fibers to determine OXPHOS capacity, fatty acid oxidation rate and the magnitude of uncoupled respiration.
Pilot data analysis revealed negative association of OXPHOS activity with age (n=14, R=–0,574, p=0,032) and BMI (n=14, R=–0,548, p=0,042) of the study volunteers. Maximal uncoupled respiration rate was also negatively associated with age (n=14, R=–0,549, p=0,042); and maximal coupled fatty acid oxidation rate (ADP-oxygen flux at RP2) was positively associated with the amount of energy (MET/min) expended by vigorous ambulatory activity during the 5 days accelerometer monitored period (Activinsights) (n=14, R=0,556, p=0,038). Moreover, fatty acid oxidation rate was also positively associated with a short-term memory (CogState) (n=14, R=0,616, p=0,019).
Pilot pre-exercise examination showed that muscle metabolism is tightly linked with age, BMI, physical activity level, but also with cognitive functions in seniors. Analyses of the other parameters is in progress and the entire complex metabolic phenotyping will be repeated after the 3-month exercise intervention.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Aging;senescence, Neurodegenerative
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS, ET Pathway: F HRR: Oxygraph-2k Event: A2
- Nemec M(1), Maderová D(1), Krumpolec P(1), Sumbalová Z(2,3), Vician M(6), Slobodová L(5), Schön M(5), Krssak M(4), Ukropcová B(1,5), Ukropec B(1,5), Ukropec J(1)
- Inst of Experimental Endocrinology, Biomedical Research Center SAS, Bratislava, SK
- Pharmacobiochemical Lab, Fac Medicine Comenius Univ, Bratislava, SK
- D. Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Medical Univ Innsbruck, AT
- High Field MR Centre, Dept Biomedical Imaging Image-guided Therapy, Medical Univ Vienna, AT
- Inst Patholog Physiol, Fac Medicine Comenius Univ, Bratislava, SK
- Dept Surgery, Slovak Medical Univ, Bratislava, SK
References and support
- Luchsinger JA (2012) Type 2 diabetes and cognitive impairment: linking mechanisms. J Alzheimers Dis 30:185-98.
- Bredesen DE (2014) Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 6:707-17.
- Tolppannen AM, Solomon A, Kulmala, J, Kareholt I, Ngandu T, Rusanen M, Laatikainen T, Soininen H, Kivipelto M (2015) Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia. Alzheimers Dement 11:434-43.
- Doerrier C, Sumbalova Z, Krumschnabel G, Hiller E, Gnaiger (2016) SUIT reference protocol for OXPHOS analysis by high-resolution respirometry. Mitochondr Physiol Network 21.06(01):1-12.