Accelerated epigenetic aging in adults with Down Syndrome in the Argentine population

Abstract

AbstractBackgroundLife expectancy of individuals with Down Syndrome (DS) is currently 60 years. From age 40 they have an increased risk of dementia and almost all of them have histopathological features of Alzheimer's disease (AD) in their brains. Also, it is known that the ε4 allele of the APOE gene and the R47H variant of TREM2 increase the risk of AD. DS is also associated with a group of clinical manifestations of accelerated aging. DNA methylation‐based biomarkers of ageing (epigenetic clocks) can be assessed by different models. It is known that DNA methylation age (DNAm) has a positive correlation with chronological age in disomic individuals while DS subjects exhibit an age acceleration effect in blood and brain.MethodWe determined the DNAm age of a cohort of seven participants with chromosome 21 trisomy (confirmed by G‐banding karyotyping). Median age was 49 years. Their cognitive status was assessed by clinical and neuropsychological evaluations. AD risk variants in APOE and TREM2 were analyzed by RFLP‐PCR. DNAm age was assessed in peripheral blood leukocytes, using the Illumina 850K platform. We used the Horvath’s epigenetic clock, based on the DNAm levels of 353 specific CpG sites.ResultFive participants exhibited the ε3/ε3 genotype in APOE and two of them the ε3/ε4 genotype. We did not observe the R47H risk variant in TREM2 in this group. Five participants showed a significant biological age acceleration and one participant’s DNAm age was similar to his chronological age. Of note, one participant showed a deceleration in the DNAm age. This participant also had multiple myeloma. It is known that the DNA methylation profile of multiple myeloma cells differs from normal plasma cells. On the other hand, we did not find a trend towards a greater presence of the risk allele ε4 or cognitive impairment in participants with a significant DNAm age acceleration.ConclusionThe majority participants presented an acceleration in their biological age, but this fact was not correlated with a greater presence of the risk allele ε4 or cognitive impairment. This is the first dataset of DNA methylation ages of a cohort of people with Down Syndrome in Latin America.