Metabolomic markers mediate erythrocyte anisocytosis in older adults: Results from three independent aging cohorts.
J Intern Med
; 293(5): 589-599, 2023 05.
Article
in En
| MEDLINE
| ID: mdl-36739565
ABSTRACT
BACKGROUND:
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.METHODS:
We performed mediation analyses of plasma metabolomics on the association between age and RDW using resampling techniques after covariate adjustment. We analyzed data from adults aged 70 or older from the main discovery cohort of the Baltimore Longitudinal Study of Aging (BLSA, n = 477, 46% women) and validation cohorts of the Health, Aging and Body Composition Study (Health ABC, n = 620, 52% women) and Invecchiare in Chianti, Aging in the Chianti Area (InCHIANTI) study (n = 735, 57% women). Plasma metabolomics was assayed using the Biocrates MxP Quant 500 kit in BLSA and Health ABC and liquid chromatography with tandem mass spectrometry in InCHIANTI.RESULTS:
In all three cohorts, symmetric dimethylarginine (SDMA) significantly mediated the association between age and RDW. Asymmetric dimethylarginine (ADMA) and 1-methylhistidine were also significant mediators in the discovery cohort and one validation cohort. In the discovery cohort, we also found choline, homoarginine, and several long-chain triglycerides significantly mediated the association between age and RDW. CONCLUSIONS AND RELEVANCE This metabolomics study of three independent aging cohorts identified a specific set of metabolites mediating anisocytosis with aging. Whether SDMA, ADMA, and 1-methylhistidine are released by the damaged erythrocytes with high RDW or they affect the physiology of erythrocytes causing high RDW should be further investigated.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiovascular Diseases
/
Erythrocytes
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Intern Med
Journal subject:
MEDICINA INTERNA
Year:
2023
Document type:
Article
Affiliation country:
United States