Insomnia accelerates the epigenetic clocks in older adults.

Abstract

Insomnia is a common sleep disorder characterized mainly by poor sleep quality and insufficient sleep duration. It affects a significant proportion of the global population and is correlated with physical and mental consequences such as cognitive decline, anxiety, chronic fatigue, poor concentration, and memory impairment. Interestingly, it is also linked to ageing and age-related diseases (cardiovascular, metabolic, and neurodegenerative). On the other hand, as we age, DNA methylation patterns undergo significant changes. These have been used to develop the so-called epigenetic clocks that estimate the biological age linked to the environment and the risk of diseases. Few studies have evaluated the association between insomnia and epigenetic clocks, providing insight into the role of insomnia in ageing acceleration. Therefore, in the present study, we carried out an epigenetic analysis by using Illumina EPICv.2 array on 63 older adults (> 60 years old, n = 33 with insomnia vs. n = 30 control) to evaluate the relation between insomnia and epigenetic ages (HorvathAGE, HannumAGE, PhenoAGE, SkinBloodClock, GrimAGE, DunedinPACE, DNAmTL). As a result, we found an increased acceleration and correlation between GrimAGE and SkinBloodClock and a significant reduction in the DNAmTL in individuals with insomnia. An EWAS analysis showed a global pattern of hypomethylation and an enrichment of several proteostasis and oxidative pathways. In conclusion, our results suggest that insomnia increases GrimAGE and SkinBloodClock acceleration and may be participating in telomere shortening. Additionally, changes in DNA methylation patterns induced by insomnia impact proteostasis and oxidative stress.