Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease.
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 homolog, 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.
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Marissa J
MJ
Schafer
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Elizabeth J
EJ
Atkinson
Medical Genome Facility-Proteomics Core, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Patrick M
PM
Vanderboom
Center for Clinical and Translational Sciences, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Brian
B
Kotajarvi
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Thomas A
TA
White
Center for Innovation, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Matthew M
MM
Moore
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Charles J
CJ
Bruce
Division of Cardiovascular Surgery, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Kevin L
KL
Greason
Division of Cardiovascular Surgery, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Rakesh M
RM
Suri
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Center for Clinical and Translational Sciences, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Division of Endocrinology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Sundeep
S
Khosla
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Division of Cardiovascular Surgery, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Jordan D
JD
Miller
Medical Genome Facility-Proteomics Core, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
H Robert
HR
Bergen
Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: lebrasseur.nathan@mayo.edu.
Nathan K
NK
LeBrasseur
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism* / Q000401:mortality; D002853:Chromatography, Liquid; D003710:Demography; D005260:Female; D055412:Growth Differentiation Factors / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055435:Myostatin / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; C525911:MSTN protein, human; D055435:Myostatin