Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

Abstract

Sarcopenia is a geriatric syndrome with a significant impact on older patients’ quality of life, morbidity and mortality. Despite the new available criteria, its early diagnosis remains difficult, highlighting the necessity of looking for a valid muscle wasting biomarker. Myostatin, a muscle mass negative regulator, is one of the potential candidates. The aim of this work is to point out various factors affecting the potential of myostatin as a biomarker of muscle wasting. Based on the literature review, we can say that recent studies produced conflicting results and revealed a number of potential confounding factors influencing their use in sarcopenia diagnosing. These factors include physiological variables (such as age, sex and physical activity) as well as a variety of disorders (including heart failure, metabolic syndrome, kidney failure and inflammatory diseases) and differences in laboratory measurement methodology. Our conclusion is that although myostatin alone might not prove to be a feasible biomarker, it could become an important part of a recently proposed panel of muscle wasting biomarkers. However, a thorough understanding of the interrelationship of these markers, as well as establishing a valid measurement methodology for myostatin and revising current research data in the light of new criteria of sarcopenia, is needed.

Salivary Testosterone and Cortisol as Biomarkers for the Diagnosis of Sarcopenia and Sarcopenic Obesity in Community-Dwelling Older Adults

“…We know of the existence of biomarkers that could potentially influence the diagnosis and development of sarcopenic disease and SO. However, due to the physiological complexity of these pathologies, it is unlikely that there is a single specific biomarker [ 6 , 7 ] that allows the identification of these diseases in the different vital stages. From this point of view, the study and development of a panel of biomarkers that can harbor direct or indirect relationships in the diagnosis and treatment of said diseases becomes relevant, and these should be easily obtained and interpreted in the clinical context as well as economically viable.…”

A Pound of Flesh: What Cachexia Is and What It Is Not

“…Theoretically, it is considered a good candidate for inclusion in the panel of muscle-wasting biomarkers. However, the use of myostatin for the diagnosis and prognosis of cachexia is affected by several issues: in particular, contradictory results regarding the correlation of its high serum levels and muscle wasting were reported in sarcopenic patients due to age and gender differences [ 67 ], while decreased serum levels of myostatin were found in patients with lung, colorectal, and medullary thyroid cancer [ 68 , 69 ]. Physical activity [ 70 ] and nutritional status [ 71 ] are also confounding factors for the adoption of myostatin as a biomarker of cachexia [ 67 ].…”

“…However, the use of myostatin for the diagnosis and prognosis of cachexia is affected by several issues: in particular, contradictory results regarding the correlation of its high serum levels and muscle wasting were reported in sarcopenic patients due to age and gender differences [ 67 ], while decreased serum levels of myostatin were found in patients with lung, colorectal, and medullary thyroid cancer [ 68 , 69 ]. Physical activity [ 70 ] and nutritional status [ 71 ] are also confounding factors for the adoption of myostatin as a biomarker of cachexia [ 67 ]. Activin is another member of the TGF-β superfamily: elevated levels of plasma activin have been proposed as an adverse prognostic factor in cancer patients [ 72 ], and its causative role in mediating catabolic responses and atrophy in muscle cells has been recently demonstrated in vitro [ 52 ].…”

“…Thus, follistatin, too, was investigated as a potential biomarker of cachexia and, especially, sarcopenia [ 73 ]. Follistatin not only binds and neutralizes myostatin but also stimulates myoblast differentiation [ 67 , 74 ]. Irisin is an exercise-induced myokine hormone that may be a useful biomarker of the muscle status in cachexia.…”

“…In summary, a number of confounding factors such as age, gender, nutritional status, and physical activity interfere with the identification of single specific diagnostic biomarkers and predictors of prognosis and therapy response with high sensitivity, specificity, and predictive power [ 67 , 82 ]. Using a panel of complementary biomarkers will help to resolve this issue.…”