Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

Kerstin Boengler, Maik Kosiol, Manuel Mayr, Rainer Schulz, Susanne Rohrbach, Kerstin Boengler, Maik Kosiol, Manuel Mayr, Rainer Schulz, Susanne Rohrbach

Abstract

Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best-known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high-energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed.

Keywords: Ageing; Caloric restriction; Heart; Mitochondria; Reactive oxygen species; Skeletal muscle.

© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1
Figure 1
ROS formation in the aged myocardium. Within mitochondria, ROS are generated from the electron transport chain (ETC), from p66Shc in the intermembrane space, and from monoamino oxidases (MAO) in the outer mitochondrial membrane. The amount of ROS generated by the ETC increases with ageing. The expression of p66Shc and MAO is enhanced with ageing, whereas the mitochondrial ROS detoxifying system (detox) is decreased with ageing. NADPH oxidase 4 (Nox4) may be present in aged cardiac mitochondria under pathophysiological conditions; however, the exact mitochondrial localization of Nox4 is unclear. The amount of ROS increases with ageing and contributes to damage of the DNA and to oxidative modifications of proteins and lipids. In the mitochondrial matrix, enhanced levels of ROS induce damage of the mitochondrial DNA (mtDNA).
Figure 2
Figure 2
Sarcopenia in aged individuals' role of mitochondria. A sedentary lifestyle significantly contributes to the progression of sarcopenia though various mito‐based mechanisms. In particular, resistance exercise training can attenuate the progression of sarcopenia, which involves also a number of changes in mitochondrial function. Whether or not a total prevention of sarcopenia can be achieved by exercise training is still a matter of debate.

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