Abstract
Aging is an intrinsic biological decline marked by multidimensional alterations spanning molecular, cellular, tissue, and organ levels. One hallmark of aging is the progressive deterioration of immune function, a condition referred to as immunosenescence. This process often involves a persistent, mild, and non-infectious inflammatory state across the body, commonly described as inflammaging. The regulation of age-related immune and inflammatory processes is critically influenced by epigenetic mechanisms, such as alterations in DNA methylation patterns, histone modifications, chromatin structure reorganization, and the regulatory actions of non-coding RNAs. Recent research has increasingly focused on the regulatory roles of post-translational modifications (PTMs), including histone methylation, acetylation, ubiquitination, and O-GlcNAcylation, have been widely recognized as fundamental modulators of immunoinflammatory processes in aging. In this review, we provide a comprehensive overview of histone modification-mediated mechanisms involved in the regulation of immunosenescence. We further highlight their functional roles from the perspective of immune inflammation and explore potential therapeutic strategies targeting histone modifications to mitigate immunosenescence.