Age-Induced Morphological, Biochemical, and Functional Alterations in Isolated Mitochondria From Murine Skeletal Muscle

Abstract

Several in vitro studies about age-associated skeletal muscle mitochondrial dysfunction are somewhat conflicting, and this might be related to different normalization procedures. The objective of this study was to normalize the functional and biochemical data per number of mitochondria present in a mitochondrial suspension. Functional and biochemical parameters were obtained in mitochondrial suspensions from murine skeletal muscle of different ages. Mitochondrial respiratory function was polarographically measured using a Clark-type oxygen electrode. Biochemical analyses included determination of citrate synthase (CS) activity and total protein content in the mitochondrial suspension. Electron microscopy analysis of the suspensions allowed calculation of the number of mitochondria per milligram of protein. Our results conclude that advanced age is associated with mitochondrial dysfunction; moreover, from the correlation between morphological and biochemical data, it is evident that CS activity in the mitochondrial suspensions is a more accurate marker of mitochondrial mass than is total protein content.

Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

“…Indeed, when matched for V O 2 max (18) or physical activity (16), skeletal muscle mitochondrial function is similar in young and older adults, suggesting that skeletal muscle mitochondrial dysfunction may not be an inherent component of senescence but rather a consequence of inactivity (27). Nevertheless, although detriments in skeletal muscle mitochondrial function may not be causal in the etiology of senescence, there is certainly strong evidence of an association (1,3,5,7,20,30,33,37). Importantly, mitochondria are responsive to environmental stimuli (11,12,14).…”

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

“…Its specific activity is frequently used as an indicator of total mitochondrial mass (Figueiredo et al, 2008;Sarnat and Marín-García, 2005;Kirby et al, 2007). Cytochrome oxidase (COX) activity is often employed as a marker of OXPHOS activity since this enzyme (complex IV) constitutes the last step in the respiratory chain (RC), likely limiting its electron flux (Capaldi, 1990;Kunz et al, 2000;Larsen et al, 2012;Mazat et al, 2001;Attardi, 1997, 2000;Villani et al, 1998).…”

Dysfonctions mitochondriales et vieillissement musculaire

“…En lien avec cette théorie, de multiples études, réalisées par la suite, s'accordèrent sur le fait que le vieillissement musculaire était associé à une augmentation de marqueurs du stress oxydant [13][14][15][16][17]. Plusieurs études ont également rapporté une augmentation de la production d'EAO par les mitochondries musculaires au cours du vieillissement chez l'homme [18,19], chez de la vitesse maximale de consommation d'oxygène, que ce soit chez l'homme [29][30][31], le rat [32][33][34][35][36], ou chez la souris [20,37]. Conley et al ont ainsi observé que le fonctionnement intrinsèque des mitochondries (c'est-à-dire leur capacité de respiration maximale) était altéré avec le vieillissement musuclaire [31].…”