Epigenetic drift and chromatin remodeling as core aging mechanisms

Epigenetics is an evolving field that is increasingly recognized as central to the understanding of biological aging. Epigenetic drift, the cumulative alteration of DNA methylation patterns, histone marks, chromatin accessibility, and three-dimensional genome organization, increasingly emerges as a molecular hallmark of aging. Decades of research have shown that these epigenetic changes are not random but correspond with diminished gene regulatory precision, impaired cellular plasticity, and a loss of tissue function. While early models suggested epigenetic drift was a passive byproduct of time, more recent studies indicate it may actively drive the development of age-associated diseases and declines in tissue homeostasis, fueling debate regarding causality and intervention potential.At the interface of these changes are epigenetic clocks, mathematical models based on DNA methylation levels that serve as highly accurate estimators of biological age. These clocks not only measure the rate of biological aging but also provide critical insights into the underlying pace of epigenetic drift across different tissues and cell types.Integral to this drift is the remodeling of chromatin: structural alterations that govern the physical state of DNA and its accessibility to transcriptional machinery. Research has demonstrated that aging involves specific shifts in chromatin organization: loss of heterochromatin, changes in nucleosome positioning, and dysregulation of chromatin-modifying enzymes, all of which contribute to aberrant gene expression, genomic instability, and even activation of harmful transposable elements. These processes do not act in isolation but intertwine with other hallmarks of aging, such as DNA damage, senescence, and metabolic shifts. Advances in single-cell and epigenomic profiling now allow precise mapping of these changes, and the emerging consensus is that understanding the interface between chromatin structure, epigenetic clocks, and epigenetic drift is vital for explaining aging at a molecular level.This Research Topic aims to uncover the mechanisms, consequences, and intervention strategies for epigenetic drift, chromatin remodeling, and epigenetic clocks in aging. The primary objective is to elucidate how age-related epigenetic changes disrupt gene regulation and to identify ways that chromatin dynamics and clock signatures can be targeted for reversing or delaying aging processes. Additional goals are to clarify the interplay between epigenetic and other molecular aging hallmarks, and to accelerate the translation of epigenetic findings into diagnostics and therapies that promote healthy lifespan.This Research Topic focuses on original and translational studies that dissect the contribution of epigenetic and chromatin-based mechanisms to aging, placing particular emphasis on regulatory, structural, and therapeutic perspectives, while not extending to unrelated molecular pathways. To gather further insights in this domain, we welcome articles addressing, but not limited to, the following themes:- DNA methylation changes and their impact on age-related gene regulation- Dynamics of histone modifications and chromatin remodeling complexes in aging- Development, optimization, and application of epigenetic clocks to measure biological age and predict healthspan- The relationship between chromatin organization, genome stability, and transposon activation- Interplay between epigenetic drift, clocks, and other cellular aging processes, such as senescence or metabolic dysfunction- Single-cell and systems biology approaches to map epigenetic aging trajectories and calibrate clock signatures- Therapeutic strategies to target, reprogram, or reverse epigenetic, clock, and chromatin changes in aging Topic editors: Zhenglong Guo, Feng Wang, Bingtao Hao Source: https://www.frontiersin.org/research-topics/83088/epigenetic-drift-and-chromatin-remodeling-as-core-aging-mechanisms