Supplementary material from "The interplay of epigenetic remodeling and transposon-mediated genomic instability in aging and longevity"

Aging and age-related diseases are the result of complex biological processes that progressively cause deterioration of cellular and tissue function. Among the key hallmarks of aging are epigenetic alterations and genomic instability, both of which are closely interconnected and significantly contribute to the aging process. The epigenome, encompassing both DNA and histone modifications, regulates gene expression and maintains genomic integrity throughout life. With age, these regulatory systems become dysregulated, leading to genome-wide changes in chromatin structure, histone modifications, and the reactivation of Transposable Elements (TEs). TEs, typically silenced in heterochromatic regions, become active in aged cells, contributing to genomic instability, mutagenesis, inflammation, and metabolic disruption. Despite their significant implications, the role of TEs in the aging process remains underexplored, the interplay between epigenomic remodeling and TE activity remains poorly understood. In this review, we explore the molecular mechanisms underlying epigenetic alterations and TE reactivation during aging, the impact of these changes on genomic stability, and the potential therapeutic interventions targeting this interplay. By deciphering the role of epigenetic modifications and TE derepression in the aging process, we aim to highlight novel avenues for anti-aging and pro-longevity strategies.