Epigenetic information loss is a common feature of multiple diseases and aging

Abstract

AbstractAging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss, especially alterations in methylation patterns, serves as a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly investigated. In this study, we mapped tissue-unique methylation patterns in both healthy and pathologically diagnosed organs. Our findings revealed that in multiple diseases and tissues, including kidney in Chronic Kidney Disease (CKD), liver in liver diseases, and adipose in Type 2 Diabetes (T2D), methylation patterns degrade in a specific manner, regressing towards the mean form observed across the body. We interpret this as epigenetic information loss, where tissue-unique patterns erode. By contrast, in pancreas of T2D patients, methylation patterns diverge away from the mean. Information loss is not limited to diseases. Sun exposure, for instance, was associated with information loss in the epidermis, but not in the dermis. Age-related erosion of unique methylation patterns was also observed in brain and breast tissues, while the colon showed divergence. Our findings demonstrate that analyzing methylation patterns in tissue-unique sites can effectively distinguish between patients and healthy controls across a range of diseases. It also underscores the role of epigenetic information loss as a common feature in various pathological conditions.Graphical abstractTissue unique methylation pattern regress toward the mean upon diseaseA single methylation site, showing low methylation in the liver and high in every other tissue, becomes more methylated in diseased livers.