Reviewing the Epigenetics of Aging

Epigenetic mechanisms regulate the pace of production of specific proteins in a cell. Feedback loops link the activities of proteins produced, input from the surrounding cell environment, and epigenetic alterations that change further production of proteins. Epigenetic control of protein production shifts constantly in response to circumstances, but many changes are characteristic of aging and the aged tissue environment. These are largely thought to be reactions to (or side effects of) underlying molecular damage such as DNA double strand breaks, or environmental change such as increased inflammatory signaling, but a minority of researchers think epigenetic change to be a significant independent cause of aging. Partial reprogramming of cells can reverse many of the epigenetic changes that are characteristic of aged cells, so tests of the hypotheses regarding the role of epigenetic change in aging will be forthcoming in the years ahead.

Epigenetic changes directly contributing to aging and aging-related diseases include the accumulation of histone variants, loss of histones and heterochromatin, and deregulated expression/activity of miRNAs. In addition, histones show aberrant post-translational modifications leading to the imbalance of activating and repressing modifications. Moreover, remodeling complexes modulate chromatin accessibility and there is an aberrant expression/activity of miRNAs. Together, these epigenetic deregulations contribute to aging-associated changes in gene transcription and, as a consequence, translation as well as the stabilization or degradation of molecular factors.

While mechanisms underlying aging-related pathologies remain to be elucidated in detail, various studies demonstrate an epigenetic component. In fact, the aforementioned epigenetic modifications were shown to play essential roles in diseases including inflammation, cancer, osteoporosis, neurodegenerative diseases, and diabetes. While the precise mechanisms and connections between several epigenetic changes and human pathologies are still poorly understood, state-of-the-art next generation sequencing methods will allow researchers to address remaining questions.

An improved understanding of epigenetic mechanisms affecting longevity will be deciding crucial step towards the identification of new potential therapeutic targets. In fact, epigenetic drugs are of particular interest to the clinic due to their reversible and transient effect. A limitation of epigenetic studies, however, are the variations among single cells (both on an individual and tissue level), which occur with an even higher frequency in aged organisms. This biologically relevant heterogeneity might be further investigated, understood and potentially deconstructed with the help of new technological approaches like single-cell genomics. Together, characterizing molecular changes in different species during aging using state-of-the-art techniques will provide key insights into the relevance of epigenetics of aging and aging-associated diseases.


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