Nemec 2017 MiP2017
Sedentary ageing accelerates the risk of neurodegenerative and metabolic diseases. Three-month supervised aerobic/strength exercise intervention to 12 seniors with/without mild cognitive impairment was performed to examine changes in the whole body metabolism and muscle mitochondrial functions in association with cognitive state.
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). Daily ambulatory activity was monitored by accelerometers (Activinsights). Biopsy of m. vastus lateralis was performed in local anaesthesia using Bergström technique and the function of muscle mitochondria was evaluated in saponin-permeabilized muscle fibers by High-Resolution Respirometry using O2k-FluoRespirometer (Oroboros Instruments, Austria). Two harmonized SUIT protocols RP1 and RP2  modified for human skeletal muscle were applied for evaluation of oxygen consumption rates expressed in pmol/(s·mg) of tissue wet weight.
Exercise training led to an increase in LEAK respiration with NADH-linked substrates pyruvate+malate (NL) (p=0.001) and ETS respiration with NADH-linked substrates+succinate (NSE) (p=0.036). The OXPHOS and ETS respiration with substrates combination octanoylcarnitine+malate+pyruvate+succinate fueling convergent electron flow from fatty acid oxidation, NADH-linked pathway and succinate (FNSP and FNSE) were elevated after the exercise as well (p=0.022 and 0.044). Rotenone-sensitive respiration was higher after the excercise in both protocols (RP1: p=0.025 and RP2: p=0.001). The increase in different mitochondrial respiration parameters was associated with higher ambulatory activity and improvements in metabolic flexibility which was documented by changes in steady state RQ (clamp; p=0.001). Improvements in metabolic flexibility were accompanied by higher NL respiration (R=0.519; p=0.023), and negatively correlated with the clamp-induced increase in energy expenditure (R= -0.510; p=0.026). Interestingly, the NL respiration was positively associated with a short-term memory (Cogstate, R=0.420; p=0.023) and negatively with the time to complete the Trail Making Test (R= -0.388; p=0.038). In addition, the OXPHOS (NP) respiration was positively associated with the score in Digital Symbol Substitution Test (R=0.388; p=0.038).
Our pilot data show that regular exercise provides benefits to the mitochondrial function and that improvements in functional state of muscle mitochondria is linked to the better metabolic and cognitive health in seniors with mild cognitive impairment.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Aging;senescence
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK Pathway: N, NS HRR: Oxygraph-2k
- Nemec M(1), Maderová D(1), Krumpolec P(1), Sedliak M(2), Cvečka J(2), Tirpáková V(3), Slobodová L(4), Schön M(4), Sumbalová Z(5,6), Ukropcová B(1,2,4), Ukropec J(1)
- Inst Exp. Endocrinol, Biomedical Research Center, Slovak Academy Sci
- Fac Physical Education Sport, Comenius Univ
- Inst Sports Medicine Physical Education, Slovak Medical Univ
- Inst Pathol Physiol
- Pharmacobiochem Lab, Fac Medicine, Comenius Univ; Bratislava, Slovakia
- Daniel Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Medical Univ Innsbruck, Austria
References and support
- 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. »»Bioblast link
- Grant support: VEGA 2/0191/15; APVV-15-0253; SAS-NSC JRC 2013/17