Myostatin and Follistatin—New Kids on the Block in the Diagnosis of Sarcopenia in IBD and Possible Therapeutic Implications

Abstract

Sarcopenia, which is a decrease in muscle strength and quality of muscle tissue, is a common disorder among patients suffering from inflammatory bowel disease. This particular group of patients often presents with malnutrition and shows low physical activity, which increases the risk of sarcopenia. Another important factor in the development of sarcopenia is an imbalanced ratio of myostatin and follistatin, which may stem from inflammation as well as genetic factors. Currently, research in this area continues, and is aimed at identifying an effective medication for the treatment of this condition. Additionally, we still have no sarcopenia markers that can be used for diagnosis. In this paper, we address the role of myostatin and follistatin as potential markers in the diagnosis of sarcopenia in patients with Crohn’s disease and ulcerative colitis, particularly in view of the genetic and biological aspects. We also present data on new perspectives in the pharmacotherapy of sarcopenia (i.e., myostatin inhibitors and gene therapy). Nevertheless, knowledge is still scarce about the roles of follistatin and myostatin in sarcopenia development among patients suffering from inflammatory bowel disease, which warrants further study.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskel

“…The myostatin-follistatin system has long been considered a possible target for sarcopenia therapies, and several clinical trials are ongoing, as reviewed by Skrzypczak and colleagues [ 37 ]. Although it is unclear whether these proteins are good biochemical markers to monitor the disease or the drug efficacy, myostatin and follistatin should be considered as a couple that helps decipher the physio-pathological drug mode of action.…”

Review article: Putting some muscle into sarcopenia—the pathogenesis, assessment and clinical impact of muscle loss in patients with inflammatory bowel disease

“…The loss of muscle is therefore thought to be secondary to an interaction between the environment and these underlying genetic predispositions. Whole genome studies, quantitative genetic mapping, DNA microarrays and microRNA studies in patients with sarcopenia have been published; unfortunately, the significant heterogeneity in the study design and genetic evaluations has led to substantial variability in the results 3 . While genes such as VDR, ACE and ACTN3 have been identified frequently in patients with sarcopenia, the clinical significance of this and the relationship of these genes in patients with IBD remain unclear and a focus for future research 3 …”

“…Myostatin, a growth differentiation factor, is known to be a negative regulator of muscle biosynthesis and homeostasis 3 . Although this protein is found mostly in skeletal muscle, it has been shown that serum levels of myostatin increase with age and are inversely proportional to lean muscle mass 3 . Of interest, this protein is found to be particularly elevated in patients with sarcopenic obesity and insulin resistance 74 .…”

“…Similarly, follistatin is an inhibitor of the transforming growth factor and plays a role in responding to environmental stresses such as oxidative stress and nutritional deficiencies. Low serum levels of follistatin may be suggestive of sarcopenia, however, given its relationship with inflammation and oxidative stress, it is unclear how specific this test will be 3 . Finally, the oncology literature has proposed the use of the neutrophil‐to‐lymphocyte ratio (NLR) as a serum marker of sarcopenia.…”

“…While sarcopenia is traditionally thought to be secondary to ageing, it is also a known complication of many chronic illnesses including cirrhosis, chronic kidney disease, neurodegenerative diseases and malignancy independent of age. [1][2][3] The most recent definitions of sarcopenia from the Asian Working Group for Sarcopenia and the European Working Group of Sarcopenia in Older People include both a loss of muscle mass and a reduction in muscle strength, utilising physical performance testing to determine severity. 2,[4][5][6] Normative values defining this loss in muscle mass or strength are published for various healthy populations.…”