Epigenetic Alterations

What it is

The epigenome is the set of chemical modifications and protein contexts that control which parts of the genome are read. It is not the DNA sequence itself, but it governs how the same genome produces a liver cell versus a neuron. With age the epigenome drifts: methylation patterns at CpG sites shift, histone marks redistribute, and chromatin loses some of its 3D organisation.

Why it matters in aging

Cells slowly lose their identity. Tissue-specific gene programmes weaken, silenced regions de-repress, and previously active programmes lose amplitude. Yamanaka-factor experiments in mice show that partial reprogramming can rejuvenate epigenetic markers and tissue function — direct evidence that the epigenome holds a meaningful component of biological age.

Mechanisms

• DNA methylation drift at CpG sites — the substrate for Horvath-type epigenetic clocks.
• Histone modification shifts — e.g. loss of repressive H3K9me3 at heterochromatin.
• Loss of heterochromatin and de-condensation of nuclear architecture.
• Altered non-coding RNA expression (miRNAs, lncRNAs).

What’s being studied

Epigenetic clocks are the most-used readout of biological age in research. Interventions that move epigenetic age in humans — including diet, exercise, and (preliminarily) rapamycin and metformin — are an active research area. Partial reprogramming in humans remains pre-clinical.

Related entries

See also: Genomic instability, Stem cell exhaustion.