Biochemistry and Biology of GDF11 and Myostatin

Walker, Ryan G.; Poggioli, Tommaso; Katsimpardi, Lida; Buchanan, Sean M.; Oh, Juhyun; Wattrus, Samuel J.; Heidecker, Bettina; Fong, Yick W.; Rubin, Lee L.; Ganz, Patricia A.; Thompson, Thomas B.; Wagers, Amy J.; Lee, Richard T.

doi:10.1161/circresaha.116.308391

Cited by 156 publications

(95 citation statements)

References 168 publications

(274 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An additional contributor to the inconsistent conclusions about GDF11’s role in aging may be the experimental contexts (e.g., species, models, doses of recombinant protein) in which it has been studied. These issues have been discussed exhaustively elsewhere (Egerman et al, 2015; Harper et al, 2016; McNally, 2016; Walker et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

et al. 2016

View full text Add to dashboard Cite

Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homologue, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, higher GDF11 at surgical baseline was associated with rehospitalization and multiple adverse events. Cumulatively, our results show that GDF11 levels do not decline throughout aging but are associated with comorbidity, frailty, and greater operative risk in older adults with cardiovascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, the study also highlighted the limitations in specificity inherent to affinity-based designs as subsequent studies have shown that the aptamer also binds myostatin (GDF8, sharing 90% sequence identity with GDF11) which may also contribute to the observed effects in mice. 69, 70 Notably, a highly specific MS study observed lower levels of GDF8 but not GDF11 with aging. 71 …”

Section: Recent Progress In Plasma Proteomics Of Cardiovascular Diseasementioning

confidence: 99%

Emerging Affinity-Based Proteomic Technologies for Large-Scale Plasma Profiling in Cardiovascular Disease

Smith¹,

2017

View full text Add to dashboard Cite

Plasma biomarkers that reflect molecular states of the cardiovascular system are central for clinical decision-making. Routinely used plasma biomarkers include troponins, natriuretic peptides and lipoprotein particles, yet interrogate only a modest subset of pathways relevant to cardiovascular disease. Systematic profiling of a larger portion of circulating plasma proteins (the plasma proteome) will provide opportunities for unbiased discovery of novel markers to improve diagnostic or predictive accuracy. In addition, proteomic profiling may inform pathophysiological understanding and point to novel therapeutic targets. Obstacles for comprehensive proteomic profiling include the immense size and structural heterogeneity of the proteome, as well as the broad range of abundance levels. Proteome-wide, untargeted profiling can be performed in tissues and cells with tandem mass spectrometry. However, applications to plasma are limited by the need for complex preanalytical sample preparation stages limiting sample throughput. Multiplexing of targeted methods based on capture and detection of specific proteins are therefore receiving increasing attention in plasma proteomics. Immunoaffinity assays are the workhorse for measuring individual proteins but have been limited for proteomic applications by long development times, cross-reactivity preventing multiplexing, specificity issues, and incomplete sensitivity to detect proteins in the lower range of the abundance spectrum (below picograms per milliliter). Emerging technologies to address these issues include nucleotide-labeled immunoassays and aptamer reagents which can be automated for efficient multiplexing of thousands of proteins at high sample throughput, coupling of affinity capture methods to mass spectrometry for improved specificity, and ultrasensitive detection systems to measure low-abundance proteins. In addition, proteomics can now be integrated with modern genomics tools to comprehensively relate proteomic profiles to genetic variants, which may both influence binding of affinity reagents and serve to validate the target specificity of affinity assays. The application of deep quantitative proteomic profiling to large cohorts has thus become increasingly feasible with emerging affinity methods. The aims of this article are to provide the broad readership of Circulation with a timely overview of emerging methods for affinity proteomics and recent progress in cardiovascular medicine based on such methods.

show abstract

“…Subsequently, GDF-11 was found to increase neurogenesis, to improve olfaction and to exert beneficial effects on the brain vasculature 81 (Table 1), as well as on aged muscle 85 . Other studies were unable to repeat these effects on systemic tissues 96 , and mass-spectrometry-based assays for GDF-11 and the related protein myostatin (GDF-8) observed no decrease in GDF-11 levels in human plasma with ageing and also found that GDF-11 levels are associated with frailty in people with cardiovascular disease 97 . Further studies will need to determine whether particular forms of GDF-11 (for example, mature, immature or post-translationally modified GDF-11) can explain these discrepancies and, most importantly, whether systemic administration of GDF-11 might be beneficial for human brains.…”

Section: Brain Rejuvenation and The Manipulation Of Ageingmentioning

confidence: 99%

Ageing, neurodegeneration and brain rejuvenation

Wyss‐Coray

2016

Nature

812

525

View full text Add to dashboard Cite

Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.

show abstract

Biochemistry and Biology of GDF11 and Myostatin

Cited by 156 publications

References 168 publications

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease

Emerging Affinity-Based Proteomic Technologies for Large-Scale Plasma Profiling in Cardiovascular Disease

Ageing, neurodegeneration and brain rejuvenation

Contact Info

Product

Resources

About