Physical performance level in sarcomeric mitochondria creatine kinase knockout mouse model throughout ageing
2021
Niel, R. | Le Moyec, L. | Launay, T. | Mille-Hamard, L. | Triba, M.N. | Maciejak, Olek | Billat, V.L. | Momken, I. | Université d'Évry-Val-d'Essonne (UEVE) | Université Paris-Saclay | Molécules de Communication et Adaptation des Micro-organismes (MCAM) ; Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) | Génétique Animale et Biologie Intégrative (GABI) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CB3S) ; Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord | Laboratoire Analyse, Modélisation et Matériaux pour la Biologie et l'Environnement (LAMBE - UMR 8587) ; Université d'Évry-Val-d'Essonne (UEVE)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY) | Signalisation et physiopathologie cardiovasculaire (CARPAT (UMRS1180)) ; Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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显示更多 [+] 显示较少 [-]英语. Purpose: The objective of the present study was to establish the role of sarcomeric mitochondrial creatine kinase (Mt-CK) in muscle energy output during exercise in a murine model of ageing (the Mt-CK knock-out mouse, Mt-CK-/-).Methods: Three age groups of Mt-CK-/- mice and control male mice (6, 9, and 18 months of age) underwent incremental treadmill running tests. The maximum speed (Vpeak) and maximal oxygen consumption (VO2 peak) values were recorded. Urine samples were analyzed using metabolomic techniques. The skeletal muscle (quadriceps) expression of proteins involved in mitochondria biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) and dynamin-related GTPase mitofusin 2 (Mnf2) were quantified.Results: The VO(2)peak (normalized to heart weight: HW) of 18-month-old (mo) Mt-CK-/- mice was 27% (p < 0.001) lower than in 18-mo control mice. The VO(2)peak/HW ratio was 29% (p < 0.001) lower in 18-mo Mt-CK-/- mice than in 6-mo (p < 0.001) and 32% (p < 0.001) than 9-mo Mt-CK-/- mice. With a 0 degrees slope, Vpeak was 10% (p < 0.05) lower in 18-mo Mt-CK-/- mice than in 6-mo Mt-CK-/- mice but did not differ when comparing the 18-mo and 6-mo control groups. The skeletal muscles weight normalized on body weight in 6-mo Mt-CK-/- were 13 to 14% (p < 0.001, p < 0.05) lower versus the 6-mo control, in addition, the presence of branched-chain amino acids in the urine of 6-mo Mt-CK-/- mice suggests an imbalance in protein turnover (catabolism rather than anabolism) but we did not observe any age-related differences. The expression of PGC-1 alpha and Mnf2 proteins in the quadriceps showed that age-related effects were more prominent than genotype effects.Conclusion: The present study showed ageing is potentialized by Mt-CK deficiency with regard to VO(2)peak, Vpeak and mitochondrial protein expression. Our results support that Mt-CK-/- mice undergo physiological adaptations, enabling them to survive and to perform as well as wild-type mice. Furthermore, it is possible that these adaptations in Mt-CK-/- mice have a high energy cost and might trigger premature ageing.
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