Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration

Lakshman, Kishore M.; Bhasin, Shalender; Corcoran, Christopher; Collins-Racie, Lisa A.; Tchistiakova, Lioudmila; Forlow, S. Bradley; Ledger, Katie St.; Burczynski, Michael E.; Dorner, Andrew J.; LaVallie, Edward R.

doi:10.1016/j.mce.2008.12.019

Cited by 99 publications

(101 citation statements)

References 36 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: 62%

“…Lower levels of 25-hydroxycholecalciferol (25OHD) were associated with severe and more progressive AAC (14,15), as well as lower myostatin levels (16). Exogenous testosterone inhibited vascular calcification and increased circulating myostatin levels (17,18). Furthermore, hemizygous deletion of the genes of type 3 and 5 collagens and of myostatin was associated with aortic dissection (19).…”

Section: Introductionmentioning

confidence: 99%

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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“…62 Previously, alterations in plasma myostatin have typically been examined in able-bodied individuals. Lakshman et al 63 reported that myostatin was lower in older (7.0 ± 0.3 ng/ml) compared to young men (8.0 ± 0.4 ng/ml), and these values were threefold lower than previously reported values 25 ranging from 20 to 30 ng/ml. This variability has been attributed to different antigen-antibody combinations found in ELISA assays used to assess myostatin levels.…”

Section: Igf-i Was Unchanged With Training Although Therementioning

confidence: 69%

Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury

Astorino

Harness

Witzke

2014

The Journal of Spinal Cord Medicine

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Spinal cord injury (SCI) induces dramatic changes in body composition including reductions in fat-free mass (FFM) and increases in fat mass (FM). Objective: To examine changes in body composition in response to chronic activity-based therapy (ABT) in persons with SCI. Design: Longitudinal exercise intervention. Methods: Seventeen men and women with SCI (mean age = 36.1 ± 11.5 years) completed 6 months of supervised ABT consisting of load bearing, resistance training, locomotor training, and functional electrical stimulation. At baseline and after 3 and 6 months of ABT, body weight, body fat, and FFM were assessed using dual-energy X-ray absorptiometry, and fasting blood samples were obtained to assess changes in insulin-like growth factor-I (IGF-I), adiponectin, and myostatin. Results: Across all subjects, there was no change (P > 0.05) in body weight, percent body fat, or FFM of the leg, arm, or trunk, whereas whole-body FFM declined (P = 0.02, 50.4 ± 8.4 to 49.2 ± 7.4 kg). No changes (P = 0.21-0.41) were demonstrated in IGF-I, adiponectin, or myostatin during the study. Conclusions: Chronic ABT focusing on the lower extremity does not slow muscle atrophy or alter body fat, body mass, or regional depots of FFM in persons with SCI. Further, it does not induce beneficial changes in adiponectin, myostatin, or IGF-I. Alternative exercise-based therapies are needed in SCI to reverse muscle atrophy and minimize the onset of related health risks.

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Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration

Cited by 99 publications

References 36 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

Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury

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