Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

Schafer, Marissa J.; Atkinson, Elizabeth J.; Vanderboom, Patrick M.; Kotajarvi, Brian R.; White, Thomas A.; Moore, Matthew M.; Bruce, Charles J.; Greason, Kevin L.; Suri, Rakesh M.; Khosla, Sundeep; Miller, Jordan D.; Bergen, H. Robert; LeBrasseur, Nathan K.

doi:10.1016/j.cmet.2016.05.023

Cited by 181 publications

(198 citation statements)

References 35 publications

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“…In this regard, some studies found higher myostatin concentrations in older men and women [11]; others found that the concentration of myostatin decreased with age in men but not in women [12-14]. Along the same lines, in some studies, muscle mass was inversely correlated with serum myostatin levels [11].…”

Section: Introductionmentioning

confidence: 74%

Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

et al. 2018

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Background: Myostatin has been proposed as a candidate biomarker for frailty and sarcopenia. However, the relationship of myostatin with these conditions remains inconclusive. Objective: To determine the association of serum myostatin concentration with body composition, physical fitness, physical activity level, and frailty in long-term nursing home residents. We also aimed to ascertain the effect of an exercise program on myostatin levels. Methods: We obtained study data on 112 participants from long-term nursing homes. Participants were randomly assigned to a control or an intervention group and performed a 6-month multicomponent exercise program. Serum myostatin levels were analyzed by ELISA. Assessments also included body composition (anthropometry and bioelectrical impedance), physical fitness (Senior Fitness Test), physical activity level (accelerometry), and frailty (Fried frailty criteria, Clinical Frailty Scale, and Tilburg frailty indicator). Results: The concentration of myostatin at baseline was positively correlated with: a leaner body composition (p < 0.05), and a higher number of steps per day and light and moderate-vigorous physical activity in women (p < 0.005); greater upper and lower limb strength, endurance, and poorer flexibility (p < 0.05) in men; and better performance (less time) in the 8-ft timed up-and-go test in both women (p < 0.01) and men (p < 0.005). We observed higher concentrations of serum myostatin in non-frail than in frail participants (p < 0.05). Additionally, we found that the implemented physical exercise intervention, which was effective to improve physical fitness, increased myostatin concentration in men (p < 0.05) but not in women. The improvements in physical condition were related with increases in serum myostatin only in men (p < 0.05–0.01). Conclusions: Higher serum levels of myostatin were found to be associated with better physical fitness. The improvements in physical fitness after the intervention were positively related to increases in myostatin concentrations in men. These results seem to rule out the idea that high serum myostatin levels are indicative of frailty in long-term nursing home residents. However, although the direction of association was opposite to that expected for the function of myostatin, the use of this protein as a biomarker for physical fitness, rather than frailty, merits further study.

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Section: Introductionmentioning

confidence: 74%

Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

et al. 2018

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“…Second, the SOMAscan is not an absolute measure of proteins, and therefore, we cannot make comparisons between proteins. Third, the accuracy of the protein specificity revealed by the SOMAscan technology is still controversial (Schafer et al., 2016). While the aptamers are designed to measure proteins in their native confirmation, there is still a possibility of cross‐reactivity for proteins with high similarity.…”

Section: Discussionmentioning

confidence: 99%

Plasma proteomic signature of age in healthy humans

Tanaka¹,

Biancotto²,

Moaddel³

et al. 2018

Aging Cell

346

349

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To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10−5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10−56). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age‐associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.

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“…Unlike myostatin, GDF11 declines in aging mice [50]. In contrast, Schafer et al [1] showed that GDF11 levels do not decline throughout aging and there was no difference between sexes in healthy adults.…”

Section: Discussionmentioning

confidence: 99%

Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men

et al. 2018

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BackgroundMyostatin, its inhibitor follistatin, and growth/differentiation factor 11 (GDF11) have been proposed as factors that could potentially modify biological aging. The study aimed to test whether there is a relationship between these plasma circulating proteins and muscle strength, power and optimal shortening velocity (υopt) of older adults.MethodsThe cross-sectional study included 56 women and 45 men aged 60 years and older. Every participant underwent examination which included anthropometric and bioimpedance analysis measurements, functional and cognitive performance tests, muscle strength of upper and lower extremities, muscle power testing with two different methods and blood analyses.ResultsWomen had higher plasma levels of myostatin and GDF11 than men. Men had higher plasma level of follistatin than women. In women, plasma level of myostatin was negatively correlated with left handgrip strength and υopt. Follistatin was negatively correlated with maximum power output (Pmax), power relative to kg of body mass (Pmax∙kg− 1) (friction-loaded cycle ergometer) and power at 70% of the 1-repetition maximum (1RM) strength value (P70%) of leg press (Keiser pneumatic resistance training equipment), and positively correlated with the Timed Up & Go (TUG) test. GDF11 was negatively correlated with body mass, body mass index, waist circumference, fat mass and the percentage of body fat. In men, there were no significant correlations observed between circulating plasma proteins and muscle function measures.ConclusionsThe circulating plasma myostatin and follistatin are negatively associated with muscle function in older women. There is stronger relationship between these proteins and muscle power than muscle strength. GDF11 has a higher association with the body mass and composition than muscle function in older women.

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Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

Cited by 181 publications

References 35 publications

Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

Plasma proteomic signature of age in healthy humans

Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men

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