The abundance, morphology, and functional properties of mitochondria decay in skeletal muscle during the process of ageing. Although the precise mechanisms remain to be elucidated, these mechanisms include decreased mitochondrial DNA (mtDNA) repair and mitochondrial biogenesis. Mitochondria possess their own protection system to repair mtDNA damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes. However, mtDNA mutations have shown to be accumulated with age in skeletal muscle. When damaged mitochondria are eliminated by autophagy, mitochondrial biogenesis plays an important role in sustaining energy production and physiological homeostasis. The capacity for mitochondrial biogenesis has shown to decrease with age in skeletal muscle, contributing to progressive mitochondrial deficiency. Understanding how these endogenous systems adapt to altered physiological conditions during the process of ageing will provide a valuable insight into the underlying mechanisms that regulate cellular homeostasis. Here we will summarize the current knowledge about the molecular mechanisms responsible for age-associated mitochondrial deficiency in skeletal muscle. In particular, recent findings on the role of mtDNA repair and mitochondrial biogenesis in maintaining mitochondrial functionality in aged skeletal muscle will be highlighted. 1. Introduction Mitochondria are ubiquitous membrane-bound organelles that are a defining and unique feature of the eukaryotic cell [1]. Mitochondria produce about 90% of the energy necessary for cellular function via oxidative phosphorylation (OXPHOS) [2]. Additionally, mitochondria play central roles in metabolism, signaling, and programmed cell death [3]. Mitochondrial deficiency has been shown in neuromuscular diseases, neurodegenerative diseases, type 2 diabetes, ageing, and sarcopenia [4–8]. During the process of ageing, the abundance, morphology, and functional properties of mitochondria decay in several tissues including skeletal muscle [9–12]. Among all cell types, the skeletal muscle possesses the unique ability to increase metabolic rate nearly 100-fold during the transition form a basal resting state to near-maximal contractile activity [11]. Thus, it is easy to assume that skeletal muscle is profoundly affected by age-associated mitochondrial deficiency. Despite age-associated mitochondrial deficiency being extensively investigated, the precise mechanisms remain to be elucidated. However, these mechanisms include at least decreased mitochondrial DNA (mtDNA) repair, defective
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