Serum Concentrations of Myostatin and Myostatin-Interacting Proteins Do Not Differ Between Young and Sarcopenic Elderly Men

Ratkevičius, Aivaras; Joyson, Amanda; Selmer, Inger-Sofie; Dhanani, Tushar; Grierson, Christal; Tommasi, A.; DeVries, A. Courtney; Rauchhaus, Petra; Crowther, Daniel; Alesci, Salvatore; Yaworsky, Paul J.; Gilbert, Fiona J.; Redpath, Thomas William; Brady, John Paul; Fearon, K. C. H.; Reid, David M.; Greig, Carolyn; Wackerhage, Henning

doi:10.1093/gerona/glr025

Cited by 90 publications

(91 citation statements)

References 43 publications

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“…Although Myostatin is doubtless an inhibitor of skeletal muscle mass development, its role in muscle atrophy remains unclear. Indeed, in contrast to early observations highlighting a link between elevated levels of Mstn and low muscularity situations,41, 42, 43 recent studies showed a decrease of circulating Myostatin in conditions characterized by reduced skeletal muscle mass such as ageing, but without correlation between Myostatin levels and muscle mass 44, 45, 46. In agreement with our results, Breitbart et al .…”

Section: Discussionsupporting

confidence: 89%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Section: Discussionsupporting

confidence: 89%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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“…Therefore, total myostatin serum levels were higher than those found using immunoassays specific for the active C-terminal dimer (18,35). In our study, total myostatin levels correlated negatively with fat mass, mainly central fat mass, but not with lean mass or grip strength (16).…”

Section: Discussioncontrasting

confidence: 63%

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Szulc¹,

Hofbauer²,

Rauner³

et al. 2012

European Journal of Endocrinology

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Objective: To assess the association between abdominal aortic calcification (AAC) and serum levels of myostatin, a negative regulator of skeletal muscle mass, which has been implicated in the development of atherosclerotic lesions in mice. Design and patients: We assessed AAC semiquantitatively from the lateral spine scans obtained using dual energy X-ray absorptiometry in 1071 men aged 20-87 years. Serum myostatin levels were measured by an immunoassay that detects all myostatin forms. Results: Total myostatin serum levels did not differ between men with or without self-reported ischemic heart disease, hypertension, or diabetes mellitus. Total serum myostatin levels were higher in men with higher serum calcium levels and lower in men with higher serum concentrations of highly sensitive C-reactive protein. Men with AAC had lower myostatin levels compared with men without AAC. Prevalence of AAC (AAC score O0) was lower in the highest myostatin quartile compared with the three lower quartiles (P!0.05). After adjustment for confounders, odds of AAC (AAC score O0) were lower (ORZ0.62; 95% confidence interval (95% CI), 0.45-0.85; P!0.005) for the fourth myostatin quartile vs the three lower quartiles combined. In the sub-analysis of 745 men aged R60 years, the results were similar: AAC prevalence was lower in the highest myostatin quartile compared with the three lower quartiles combined (ORZ0.54; 95% CI, 0.38-0.78; P!0.001). Conclusions: In older men, total myostatin serum levels are inversely correlated with AAC. Further studies are needed to investigate mechanisms underlying this association and to assess utility of myostatin as a cardiovascular marker.

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“…Yet, data for the relationship between circulating myostatin and agerelated muscle loss have been scarce and conflicting. While an earlier study reported significant elevations in serum myostatin levels with advancing age and declining lean mass (Yarasheski et al 2002), more recent studies had failed to support these findings (Hofmann et al 2015;Ratkevicius et al 2011). Intriguingly, we have observed myostatin to confer deleterious effects for sarcopenia only in older male adults that, if corroborated, has important clinical significance in selection of individuals most likely to benefit from myostatin blocking therapy.…”

Section: Discussionmentioning

confidence: 43%

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

Tay

Ding

Leung

et al. 2015

AGE

140

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With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this crosssectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, Creactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR=5.71, 95 % CI 1.13-28.84.44, p=0.035) while higher but acceptable range serum triglyceride was protective in men (OR=0.05, 95 % CI 0.00-0.52, p=0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR=1.11, 95 % CI 1.00-1.24, p=0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1 % decline in odds of sarcopenia in women (p=0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

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Serum Concentrations of Myostatin and Myostatin-Interacting Proteins Do Not Differ Between Young and Sarcopenic Elderly Men

Cited by 90 publications

References 43 publications

Circulating Activin A predicts survival in cancer patients

Circulating Activin A predicts survival in cancer patients

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults

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