DNA Methylation and Health Outcome in an Aging Cohort

Abstract

DNA methylation undergoes extensive remodeling over the course of life, and is considered to be a biomarker of human age and potentially predictive of health and lifespan. Here, we track changes in DNA methylation over time and its significance with regards to healthy aging. Using principle component analysis, we found: PC1 is strongly correlated with blood cell type, PC1 captures lymphoid and granulocyte signal, this signal is robust specific to blood cell type, and PC1 is significantly associated with cancer outcome at both visit years 1 and 6. Primary cancer sites include: leukemia, prostate, colon, breast, and stomach. There was no greater age acceleration in the cancer group, and the methylation age for all samples increased over time. While the methylation age appears significantly older than the actual chronological age, our analysis shows that the methylation age is sensitive enough to capture longitudinal age progression over the course of 5 years. Our data demonstrates that we can derive information on cellular composition and change in cellular composition with age from global patterns in DNA methylation. The methylation pattern may also be predictive of future cancer diagnosis.