Abstract
Aging represents the multifactorial decline in physiological function of every living organism. Over the past decades, several hallmarks of aging have been defined, including epigenetic deregulation. Indeed, multiple epigenetic events were found altered across different species during aging. Epigenetic changes directly contributing to aging and aging-related diseases include the accumulation of histone variants, changes in chromatin accessibility, loss of histones and heterochromatin, aberrant histone modifications, and deregulated expression/activity of miRNAs. As a consequence, cellular processes are affected, which results in the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, and neurodegenerative disorders. In this review, we focus on epigenetic mechanisms underlying aging-related processes in various species and describe how these deregulations contribute to human diseases.
Highlights
Aging is a multifactorial biological process of declining physiological functions increasing the susceptibility to aging-related chronic diseases, such as cancer, metabolic, cardiovascular, musculoskeletal, as well as neurodegenerative diseases [1]
This review provides a comprehensive overview of the key role of epigenetic mechanisms in controlling aging as well as the development of aging-associated pathologies
It has been shown that distinct epigenetic mechanisms are enriched in aging organisms including the accumulation of histone variants as well as the loss of histones and heterochromatin (Figure 1)
Summary
Aging is a multifactorial biological process of declining physiological functions increasing the susceptibility to aging-related chronic diseases, such as cancer, metabolic, cardiovascular, musculoskeletal, as well as neurodegenerative diseases [1]. Numerous studies have focused on the decipherment of the hallmarks of aging in order to identify potential therapeutic targets to mitigate the aging process. Epigenetics refers to reversible heritable mechanisms, which can affect gene expression without underlying changes in DNA sequences, but rather via chromatin modifications. These tails can be subjected to post-translational modifications, which frequently affect gene expression. These modifications include, for instance, histone acetylation, methylation, phosphorylation and ubiquitination [5]. Epigenetics is a rapidly evolving research field and there is a profound interest in therapies targeting epigenetic as well as aging-related processes. We focus on aging-associated epigenetic regulatory mechanisms and highlight their implications in aging-related diseases
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