Powerful signals for weak muscles.
The aim of the present review is to summarise, evaluate and critique the different mechanisms involved in anabolic growth of skeletal muscle and the catabolic processes involved in cancer cachexia and sarcopenia of ageing. This is highly relevant, since they represent targets for future promising clinical investigations. Sarcopenia is an inevitable process associated with a gradual reduction in muscle mass and strength, associated with a reduction in motor unit number and atrophy of muscle fibres, especially the fast type IIa fibres. The loss of muscle mass with ageing is clinically important because it leads to diminished functional ability and associated complications. Cachexia is widely recognised as severe and rapid wasting accompanying disease states such as cancer or immunodeficiency disease. One of the main characteristics of cancer cachexia is asthenia or lack of strength, which is directly related to the muscle loss. Indeed, apart from the speed of loss, muscle wasting during cancer and ageing share many common metabolic pathways and mediators. In healthy young individuals, muscles maintain their mass and function because of a balance between protein synthesis and protein degradation associated with rates of anabolic and catabolic processes, respectively. Muscles grow (hypertrophy) when protein synthesis exceeds protein degradation. Conversely, muscles shrink (atrophy) when protein degradation dominates. These processes are not occurring independently of each other, but are finely coordinated by a web of intricate signalling networks. Such signalling networks are in charge of executing environmental and cellular cues that ultimately determine whether muscle proteins are synthesised or degraded. Increasing our understanding for the pathways involved in hypertrophy and atrophy and particularly the interaction of these pathways is essential in designing therapeutic strategies for both prevention and treatment of muscle wasting conditions with age and with disease.
Saini
Amarjit
A
Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, United Kingdom. a.saini@mmu.ac.uk
Faulkner
Steve
S
Al-Shanti
Nasser
N
Stewart
Claire
C
D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D018908:Muscle Weakness / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology
D009124:Muscle Proteins