ABSTRACT
Endurance exercise is not only a panacea to prevent and treat many lifestyle-related diseases but also the main tool to condition endurance athletes for events such as the Ironman Triathlon World Championships in Hawaii, the Tour de France, city marathons and winter climbs in Scotland. In this chapter, we will first explore whether common endurance training recommendations (for example how hard and how long one should train) can be backed up by sound scientific evidence. We show that there is little reliable, epidemiological evidence for many training recommendations and also highlight that the training response to a given training programme varies considerably among individuals. With this background, the rest of the chapter centres on the question ‘What are the molecular mechanisms that mediate the adaptation of especially skeletal and cardiac muscle to endurance exercise?’ First, we will discuss the mechanisms that are responsible for the development of an athlete’s heart and compare the molecular events that drive the genesis of the athlete’s heart with those associated with the disease state we know as hypertrophic cardiomyopathy. Second, we will describe type I, IIb, IIx and IIb muscle fibres. Even though this is a focus of much discussion in the training and performance world, we will show that the effect of endurance exercise on muscle fibre type percentages is small and usually only involves a reduction in type IIx fibres and increase in IIa fibres. We will also discuss how calcineurin-NFAT signalling differs between fast and slow muscle fibres and how this affects fibre type-specific gene expression. ird, we specifically look at the evolutionary conserved genomic organization of myosin heavy chain isoform genes in a fast and slow gene cluster. We review how MyoMir-Sox6 signalling contributes to the on/off signalling of these genes to ensure that most of the time only one myosin heavy chain isoform is expressed in a muscle fibre. As part of this discussion, we also show how the DNA of exercise-responsive genes is opened up or closed by epigenetic mechanisms such as methylation. Fourth, we discuss how increased energy turnover and other signals are sensed by CaMK, AMPK and SIRT1 and lead to the activation of these proteins. Active CaMK, AMPK and SIRT1 then activate the transcriptional co-factor PGC-1D via multiple mechanisms. PGC-1D regulates the expression of mitochondrial genes encoded in nuclear and of transcription factors that increase the expression of genes encoded in mitochondrial DNA (mtDNA). Finally we discuss how AMPK-PGC-1D, HIF-1 and nitric oxide (NO) regulate exercise-induced angiogenesis by affecting the expression of growth factors such as VEGF and of metalloproteinases that tunnel into the extracellular matrix so that endothelial cells can form capillaries in these tunnels.
