Sandu, A.-L. | Search bioRxiv

bioRxiv2023

The influence of birthweight, socioeconomic status, and adult health on brain volumes during aging

Preserved late-life brain volume is associated with resilience to dementia. We examined relationships between birthweight, socioeconomic status and adult health with late-life brain volumes. We hypothesised that early-life factors have direct and indirect effects on the aging brain. Neurotypical adults aged 61-67y underwent MRI and brain volumes measured. Birthweight, health and socioeconomic status were assessed by historical data or contemporary assessment. Measures of health and socioeconomic status were extracted using principal component analysis. Relationships between variables were explored by linear regression and structural equation models. Birthweight ({beta}=0.095, p=0.017, n=280) and childhood socioeconomic status ({beta}=0.091, p=0.033, n=280) were directly associated with late-life brain volume. Childhood socioeconomic status was associated with additional increase in grey matter volume ({beta}=0.04, p=0.047, n=280). Better adult health was linked to increased late-life brain volume ({beta}=0.15, p=0.003, n=280). Birthweight and childhood socioeconomic status are associated with whole and regional brain volume through direct and indirect mechanisms. Optimal fetal development, good adult health and reduced poverty, may prevent brain atrophy and decrease dementia risk in late-life.

neuroscience↗

bioRxiv2021

Local CpG density affects the trajectory of age-associated epigenetic changes

DNA methylation is an epigenetic mark associated with gene repression and genome stability. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Rates of aging inferred from these clocks correlate with human health. However, the molecular mechanisms underpinning age-associated DNA methylation changes are unknown. Local DNA sequence plays a strong role in programming DNA methylation levels at individual loci independently of age, but its influence on age-associated DNA methylation changes is unknown. We analysed longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs in the genome. We show that changes in methylation with age are especially apparent at 8,322 low CpG density loci. Using SNP data from the same individuals we demonstrate that DNA methylation trajectories are affected by local sequence polymorphisms at 1,487 loci with low CpG density. More generally, we find that local CpG density is a strong determinant of a CpGs methylation trajectory and that CpGs located in low CpG density regions are particularly prone to change. Overall, our results demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.

genetics↗