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==Publications== {{medline-entry |title=Relationship of Circulating Growth and Differentiation Factors 8 and 11 and Their Antagonists as Measured Using Liquid Chromatography-Tandem Mass Spectrometry With Age and Skeletal Muscle Strength in Healthy Adults. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30380014 |abstract=Growth and differentiation factors 8 (GDF8) and 11 ([[GDF11]]) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be affected by circulating antagonists such as their respective prodomains, follistatin (FST315), [[WFIKKN1]], and [[WFIKKN2]]. Reports of the relationship of GDF8 and [[GDF11]] and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides. Plasma GDF8 and [[GDF11]] and their antagonists were measured using a multiplexed selected reaction monitoring assay and liquid chromatography-tandem mass spectrometry in 160 healthy adults aged 22-93 years. Quadriceps strength was measured by knee extensor torque using isokinetic dynamometry. Spearman correlations with age were the following: [[GDF11]] prodomain (r = .30, p = .001), [[GDF11]] mature protein (r = .23, p = .004), FST315 (r = .32, p < .0001), [[WFIKKN1]] (r = -.21, p = 0.008), and [[WFIKKN2]] (r = .18, p = .02). Independent of age, FST315 and [[WFIKKN1]] were negatively associated with knee strength (p = .02, p = .03, respectively) in a multivariable model that included both GDF8 and [[GDF11]] mature proteins. When measured by an antibody-free selected reaction monitoring assay, GDF8, [[GDF11]], and their antagonists are found in the circulation in the ng/mL range. In healthy adults, plasma [[GDF11]] and antagonists FST315, [[WFIKKN1]], and [[WFIKKN2]] differed by age. Antagonists of GDF8 and [[GDF11]], but not GDF8 and [[GDF11]], were independently associated with skeletal muscle strength. Further work is needed to characterize the relationship of these protein and polypeptides with sarcopenia-related phenotypes such as physical function and walking disability. |mesh-terms=* Adult * Aged * Aged, 80 and over * Aging * Biomarkers * Bone Morphogenetic Proteins * Carrier Proteins * Chromatography, Liquid * Female * Follistatin * Growth Differentiation Factors * Healthy Volunteers * Humans * Intercellular Signaling Peptides and Proteins * Male * Middle Aged * Muscle Strength * Muscle, Skeletal * Myostatin * Proteins * Tandem Mass Spectrometry * Young Adult |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298188 }} {{medline-entry |title=A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28508553 |abstract=Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), [[GDF11]], eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and [[GDF11]] have known antagonists such as follistatin ([[FST]]), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing proteins 1 and 2 ([[WFIKKN1]], [[WFIKKN2]]). We developed a novel multiplexed [[SRM]] assay using LC-MS/MS to measure five proteins related to GDF8 and [[GDF11]] signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting of 54 transitions were monitored and validated in pooled human plasma. In 24 adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide, 11.0 (2.4); GDF8 mature protein, 25.7 (8.0); [[GDF11]] propeptide, 21.3 (10.9); [[GDF11]] mature protein, 16.5 (12.4); [[FST]], 29.8 (7.1); [[FST]] cleavage form [[FST]]303, 96.4 (69.2); [[WFIKKN1]], 38.3 (8.3); [[WFIKKN2]], 32.2 (10.5); oxytocin, 1.9 (0.9); and eotaxin, 2.3 (0.5). This novel multiplexed [[SRM]] assay should facilitate the study of the relationships of these proteoforms with major aging phenotypes. |mesh-terms=* Aging * Biomarkers * Bone Morphogenetic Proteins * Carrier Proteins * Chemokine CCL11 * Female * Growth Differentiation Factors * Humans * Intercellular Signaling Peptides and Proteins * Male * Middle Aged * Myostatin * Oxytocin * Phenotype * Protein Isoforms * Proteins * Proteome * Proteomics |keywords=* Aging * Eotaxin * Follistatin * Growth/differentiation factor 11 * Growth/differentiation factor 8 * Oxytocin * WFIKKN1 * WFIKKN2 |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863538 }}
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