Metabolomic markers mediate erythrocyte anisocytosis in older adults: Results from three independent aging cohorts

Anisocytosis reflects unequal‐sized red blood cells and is quantified using red blood cell distribution width (RDW). RDW increases with age and has been consistently associated with adverse health outcomes, such as cardiovascular disease and mortality. Why RDW increases with age is not understood. We aimed to identify plasma metabolomic markers mediating anisocytosis with aging.

[1]  M. Wojtkowski,et al.  Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall , 2022, Scientific Reports.

[2]  K. Haile,et al.  Red Blood Cell Distribution Width as Novel Biomarker in Cardiovascular Diseases: A Literature Review , 2022, Journal of blood medicine.

[3]  L. Ferrucci,et al.  Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function , 2022, GeroScience.

[4]  J. Beckman,et al.  Using genetics to detangle the relationships between red cell distribution width and cardiovascular diseases: a unique role for body mass index , 2021, Open Heart.

[5]  L. Ferrucci,et al.  Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging , 2021, Metabolomics.

[6]  Xander M R van Wijk,et al.  Evaluation of Biomarkers in Sepsis: High Dimethylarginine (ADMA and SDMA) Concentrations Are Associated with Mortality. , 2020, The journal of applied laboratory medicine.

[7]  J. Elliott,et al.  The new age of renal biomarkers: does SDMA solve all of our problems? , 2020, The Journal of small animal practice.

[8]  S. Hinkle,et al.  Dietary Patterns and Renal Health Outcomes in the General Population: A Review Focusing on Prospective Studies , 2019, Nutrients.

[9]  J. Rodriguez-Perez,et al.  Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach , 2019, International journal of molecular sciences.

[10]  A. Newman,et al.  Metabolites Associated with Vigor to Frailty Among Community-Dwelling Older Black Men , 2019, Metabolites.

[11]  D. Melzer,et al.  Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years , 2018, PloS one.

[12]  J. Linseisen,et al.  Plasma concentrations of anserine, carnosine and pi-methylhistidine as biomarkers of habitual meat consumption , 2018, European Journal of Clinical Nutrition.

[13]  D. Fliser,et al.  Symmetric dimethylarginine (SDMA) outperforms asymmetric dimethylarginine (ADMA) and other methylarginines as predictor of renal and cardiovascular outcome in non-dialysis chronic kidney disease , 2018, Clinical Research in Cardiology.

[14]  D. Tsikas,et al.  Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and homoarginine (hArg): the ADMA, SDMA and hArg paradoxes , 2018, Cardiovascular Diabetology.

[15]  A. Jayyousi,et al.  Red Cell Distribution Width Is Associated with All-Cause and Cardiovascular Mortality in Patients with Diabetes , 2017, BioMed research international.

[16]  Q. Tang,et al.  Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases , 2017, Disease markers.

[17]  A. Naska,et al.  A metabolomic study of biomarkers of meat and fish intake. , 2017, The American journal of clinical nutrition.

[18]  W. Lieb,et al.  Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies , 2016, PloS one.

[19]  J. Hoffmann,et al.  Effect of age and gender on reference intervals of red blood cell distribution width (RDW) and mean red cell volume (MCV) , 2015, Clinical chemistry and laboratory medicine.

[20]  G. Lippi,et al.  Red blood cell distribution width and cardiovascular diseases. , 2015, Journal of thoracic disease.

[21]  A. Vayá,et al.  Influence of age and gender on red blood cell distribution width , 2015, Clinical chemistry and laboratory medicine.

[22]  G. Lippi,et al.  Red blood cell distribution width is significantly associated with aging and gender , 2014, Clinical chemistry and laboratory medicine.

[23]  H. Shang,et al.  Complete blood count reference intervals and age- and sex-related trends of North China Han population , 2014, Clinical chemistry and laboratory medicine.

[24]  F. Kronenberg,et al.  Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study , 2013, PloS one.

[25]  M. Davids,et al.  Role of the human erythrocyte in generation and storage of asymmetric dimethylarginine. , 2012, American journal of physiology. Heart and circulatory physiology.

[26]  W. März,et al.  Low homoarginine concentration is a novel risk factor for heart disease , 2011, Heart.

[27]  J. Boffa,et al.  Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF‐β1 synthesis , 2011, The Journal of pathology.

[28]  L. Keele,et al.  A General Approach to Causal Mediation Analysis , 2010, Psychological methods.

[29]  S. Bandinelli,et al.  Red cell distribution width and mortality in older adults: a meta-analysis. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[30]  L. Allen,et al.  Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure. , 2010, Journal of cardiac failure.

[31]  F. Palm,et al.  Cellular ADMA: regulation and action. , 2009, Pharmacological research.

[32]  L. Ferrucci.  The Baltimore Longitudinal Study of Aging (BLSA): a 50-year-long journey and plans for the future. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[33]  E. Schwedhelm,et al.  High-throughput liquid chromatographic-tandem mass spectrometric determination of arginine and dimethylated arginine derivatives in human and mouse plasma. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[34]  J. Cooke,et al.  Symmetric dimethylarginine (SDMA) as endogenous marker of renal function--a meta-analysis. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[35]  Frank Herrmann,et al.  Dynamics of Human Protein Arginine Methyltransferase 1(PRMT1) in Vivo* , 2005, Journal of Biological Chemistry.

[36]  L. Ferrucci,et al.  Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study. , 2005, Archives of internal medicine.

[37]  S. Richard,et al.  Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5). , 2005, The Biochemical journal.

[38]  J. Cooke.  Asymmetrical Dimethylarginine: The Über Marker? , 2004, Circulation.

[39]  Luigi Ferrucci,et al.  Subsystems Contributing to the Decline in Ability to Walk: Bridging the Gap Between Epidemiology and Geriatric Practice in the InCHIANTI Study , 2000, Journal of the American Geriatrics Society.

[40]  T. Myint,et al.  Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists. , 2000, American journal of epidemiology.

[41]  Ian G. Charles,et al.  Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. , 1999, The Biochemical journal.

[42]  I. Rossman,et al.  Normal Human Aging: The Baltimore Longitudinal Study of Aging , 1986 .

[43]  D. Rutledge,et al.  Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans , 2019, Molecular nutrition & food research.

[44]  K. Patel,et al.  Association of the red cell distribution width with red blood cell deformability. , 2013, Advances in experimental medicine and biology.

[45]  William E Grizzle,et al.  Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. , 2009, Journal of proteome research.

[46]  E. Okuma,et al.  Human urinary excretion of L-histidine-related compounds after ingestion of several meats and fish muscle. , 1993, The International journal of biochemistry.

[47]  G. Friman,et al.  Evaluation of urinary 3-methylhistidine excretion in infection by measurements of 1-methylhistidine and the creatinine ratios. , 1989, The American journal of clinical nutrition.