Brain and Nerve

Long-Term Effects of Epigenome Memory on Physiological Function in Aging

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Abstract

The epigenome, a dynamic regulator of gene expression, has emerged as a key mediator of long-term cellular and organ functions. Beyond its classical role in gene regulation, the epigenome serves as a molecular "memory", capturing external environmental influences, such as lifestyle factors, obesity, and stress-induced DNA damage. Epigenomic memory can imprint persistent changes in cellular identity and functionality, thereby influencing aging and the onset of age-related diseases. Recent studies have revealed that early-life stress-induced DNA damage can accelerate aging by establishing epigenomic memory. However, strategies aimed at "rejuvenation", the targeted resetting of epigenomic information, are gaining traction for their potential to reverse aging phenotypes and treat diseases. This review explores the concept of the epigenome as a memory system, its role in aging, and emerging therapeutic approaches to rejuvenation.