Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment

Highlights

• Updates on mechanisms of loss of muscle mass

• Current developments in biomarker research for muscle mass

• Update on new treatment developments to increase muscle mass

Abstract

Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartrate-resistant acid phosphatase 5a (TRACP5a), and novel substances like Epigallocatechin-3-gallate (EGCg). In summary, the progress to combat muscle wasting is in full swing and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon supported by improved and more helpful strategies.

Introduction

Loss of muscle mass is commonly observed in chronic diseases like cancer, chronic heart failure (HF), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cystic fibrosis, liver cirrhosis, Crohn's disease, rheumatoid arthritis, stroke and many neurodegenerative diseases as well as in HIV/AIDS, malaria, and tuberculosis [1], [2], [3]. A serious complication of these chronic illnesses is cachexia. Cachexia is defined as weight loss greater than 5% of body weight in 12 months or less in the presence of chronic illness or as a body mass index (BMI) lower than 20 kg/m². In addition, usually three of the following five criteria are required: decreased muscle strength, fatigue, anorexia, low fat-free mass index, increase of inflammation markers such as C-reactive protein or interleukin (IL)-6 as well as anemia or low serum albumin [4], [5]. Loss of muscle mass and function, especially muscle strength and gait speed, associated with aging occur in sarcopenia [6], [7]. Indeed, sarcopenia, cachexia and malnutrition are considered as the main causes of muscle wasting [8] and affect millions of elderly people and patients [9]. Moreover, muscle atrophy can develop independently from diseases and age through disuse of the muscles [10]. For a better classification and common language in medical science for “muscle wasting disease” there is a proposal to combine the concepts of muscle wasting, sarcopenia, frailty and cachexia by disease etiology and disease progression [8]. Patients with muscle atrophy show decreased muscle strength and therefore reduced quality of life, which is caused by a lower activity and increased exercise intolerance [11]. In sarcopenic patients, muscle wasting is frequently associated with loss of bone, which leads to a higher risk of hip and other fractures [12]. Hip fracture also results in loss of musculature due to disuse atrophy [13]. All these conditions lead to increased morbidity and mortality in patients [14], and therefore developments in biomarkers and treatment finding to improve patients' lives is necessary (for schematic representation of the process see Fig. 1). The reason for muscle atrophy is an imbalance of protein synthesis and protein degradation. Three major protein degradation pathways play a role in development of muscle wasting: (1) activation of the ubiquitin–proteasome-system (UPS), (2) apoptosis through caspase signaling and (3) autophagy [15].