Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness

Abstract

BackgroundThe skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults.MethodsBaseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week.ResultsAt baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism ,and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73).ConclusionsOur data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle.

Skeletal muscle wasting in chronic heart failure

“…74 Currently, there are only few therapy options for patients suffering from sarcopenia, which include (resistance) exercise, 75-77 nutritional approaches to increase consumption of proteins and micronutrients, 78,79 and finally, drug treatment, including testosterone, 80,81 growth hormone (GH), and IGF-1. 90 Exercise training has been acknowledged as an evidencebased therapeutic approach with prognostic benefits in cardiovascular illness including CHF, as it improves risk factors such as hyperlipidaemia, hypertension, and coronary endothelial function. 46,83-85 Supplementation of a low-dose creatine in combination with resistance training improved lean mass in elderly over a period of 12 weeks.…”

“…89 Interestingly, a significant plasticity of ageing skeletal muscle to adapt to resistancetype exercise training has been shown by transcriptomics after a 6 month training period including partial reversal of age-related changes in skeletal muscle gene expression. 90 Exercise training has been acknowledged as an evidencebased therapeutic approach with prognostic benefits in cardiovascular illness including CHF, as it improves risk factors such as hyperlipidaemia, hypertension, and coronary endothelial function. 91 Exercise training not only has cardio-protective effects and thereby attenuates the progression from cardiac dysfunction to CHF but also induces anticatabolic signalling in skeletal muscle, possibly by stimulation of PGC1α.…”

Skeletal muscle performance and ageing

“…For example, the levels of physical activity and nutritional intake are important lifestyle factors 7,8 and genetics, hormones, and low-grade inflammation are examples of biological factors. [9][10][11][12] Psychosocial factors, such as fear of falling, 13 psychological resiliency, 14 self-efficacy, 15 and loneliness, 16 are also direct and indirect determinants of elderly skeletal muscle performance.…”

Contemporary publication patterns in the Journal of Cachexia, Sarcopenia and Muscle by type and sub‐speciality: facts and numbers

“…[12][13][14][15][16][17] In the area of translational studies in the mechanisms of cachexia, studies were published on expression of spliced skeletal muscle genes, 18 along with scientific evaluations of skeletal muscle physiology, 19,20 growth, wasting, 21-23 preservation, 24,25 and regeneration. For the first time, the journal was seeing Cochrane reviews of the evidence base for interventions in cachexia and related fields coming through.…”

“…8,9 One of the strongest emerging fields are detailed clinical series of ageing effects, both detailed physiological evaluations 10,11 and large scale cohort reports. [12][13][14][15][16][17] In the area of translational studies in the mechanisms of cachexia, studies were published on expression of spliced skeletal muscle genes, 18 along with scientific evaluations of skeletal muscle physiology, 19,20 growth, wasting, 21-23 preservation, 24,25 and regeneration. 26 Basic science approaches were also used to study the growing interest in the cardiac and cardio-metabolic effects of cancerrelated cachexia and of modern cancer therapies.…”