Sleep and aging: The role of DNA methylation.

Although its evolutionary origins remain poorly understood, sleep is a highly conserved physiological process crucial to animal life and widely recognized as a major determinant of human healthspan. Sleep disturbances are a major public health concern, particularly among older adults, contributing to impaired cognitive function, chronic disease risk, and reduced quality of life. Age-related sleep disturbances are associated with epigenetic changes, especially altered DNA methylation patterns within genes and regulatory regions involved in circadian rhythms, neuroplasticity, metabolism, and inflammation. Over the past decade, epigenetic clocks, which measure DNA methylation patterns at specific CpG sites, have been used to estimate chronological age, assess biological aging, and predict health outcomes and mortality risk. Using epigenetic clocks and genome-wide methylation studies, emerging evidence has linked sleep disturbances and sleep-disrupting conditions, such as insomnia, obstructive sleep apnea, and shift work, to accelerated biological aging. Sleep-related changes in DNA methylation contribute to epigenetic age acceleration by influencing key aging processes, including inflammation, oxidative stress, telomere maintenance, lipid metabolism, and immune function. However, these methylation alterations might be, at least in part, reversible, highlighting opportunities to develop interventions that improve sleep disturbances and slow biological aging.