356-OR: DNA Methylation Suggests Accelerated Biological Age and Specific Biomarkers Correlate with the Speed of Aging in Diabetes Mellitus

Abstract

Type 2 Diabetes (T2D) correlates with increased biological age (BA) as indicated by clinical biomarkers. Chronological age (CA) is the total years lived, while BA depicts cellular level changes. Our prior data showed that BA was accelerated in Type 1 Diabetes (T1D) and T2D with a large spread of individual BA within these groups. It is unknown whether accelerated age in diabetes mellitus (DM) is also seen at the DNA methylation (DNAm) level, the gold standard to determine BA, and which variables regulate the speed of aging in individuals. We hypothesized that DNAm would reflect accelerated aging in tissues from people with T2D and that specific biomarkers would associate with the speed of aging. The DNAm Phenotypic Age Clock was used to determine BA and showed accelerated aging in whole blood (p=0.01) and pancreatic islets (p=0.03) from people with T2D. Linear regression was used to find associations between biomarkers and speed of aging using the NHANES 2017-18 and ACCORD Trial cohorts. Avoidance of fried foods (p=0.02) and fat intake (p=0.01) , and vigorous activity (p=0.001) correlated with decreased BA in T2D. Biomarkers associated with slower aging (BA<5 years from CA) were higher albumin (p<0.04) , lower globulin (p=5.7x10-5) , lower blood pressure (p<0.005) , higher hemoglobin (p<0.03) and older age at DM diagnosis (p=0.04) . Faster aging (BA>5 years from CA) was associated with higher total and LDL-cholesterol (p<0.003) , pulse (p=0.002) , platelet count (p<0.03) , glycohemoglobin (p<3.6x10-5) and fasting glucose (p<0.04) , and lower self-perception of health (p=0.005) . Normal aging (BA within 5 years of CA) associated with greater ferritin (p=0.03) and moderate-intensity activity at work (p=0.005) . In conclusion, DNAm of blood and islets from people with T2D age faster than those without. Further analysis of specific variables associated with the speed of aging will identify crucial intervention nodes to alter the aging speed in a population with DM. Disclosure B.N.Cortez: None. H.Pan: n/a. C.Aguayo-mazzucato: Consultant; eGenesis.