Epigenetics controls which genes are active, through DNA methylation, histone modification and microRNA, without changing the DNA sequence. Epigenetic abnormalities have a proven role in cancer and other diseases. Reversal through medicines has already been applied clinically in certain blood cancers, but applications in ageing and prevention in healthy people remain experimental.
Epigenetics is the field of study that examines how genes can be switched on or off without changing the actual sequence of the DNA itself. This happens through three key mechanisms: DNA methylation (a chemical 'flag' on the DNA that can silence a gene), histone modification (histones are the protein spools around which DNA is wound; changes to them determine how accessible a gene is) and microRNA (small pieces of genetic material that fine-tune gene activity). These changes can be passed on to daughter cells during cell division, making them heritable at the cellular level, even though they do not affect the DNA sequence.
The importance of epigenetics for health is considerable. When epigenetic regulation goes wrong, serious diseases can develop. In cancer, disrupted DNA methylation and histone modifications are a common feature that contributes to tumour formation and growth. Auto-immune diseases and other conditions have also been linked to epigenetic abnormalities. In cancer, metabolism plays an additional role: products of metabolic processes can activate or inhibit epigenetic enzymes, further disrupting gene expression.
A hopeful aspect of epigenetics is that epigenetic changes are in principle reversible, unlike true DNA mutations. Medicines have already been developed that specifically target epigenetic mechanisms. In certain forms of lymphoma (a type of blood cancer) and pre-leukaemia, these drugs are showing promising results. For solid tumours (such as lung cancer or bowel cancer), early positive results are also emerging, but research there is still in its infancy.
The epigenome also changes naturally with age. DNA methylation patterns shift, histones are modified differently and the way DNA is packaged inside the cell nucleus changes. These shifts are associated with the deterioration of tissues and organs and an increased risk of age-related diseases. Researchers are exploring strategies to 'rejuvenate' this aged epigenome, through metabolic adjustments, partial genetic reprogramming or medicines. Knowledge is growing rapidly, but this is still early-stage scientific research, largely in animal models. Reliable applications for healthy people are not yet available.
Finally, epigenetic changes have also been found in specific conditions such as asthma: DNA methylation patterns in airway cells differ from patient to patient and from one cell type to another. These patterns are associated with processes such as airway remodelling and immune responses. Whether and how these epigenetic changes directly influence the course of asthma, however, is not yet sufficiently understood.
The basic biology of epigenetics (mechanisms, role in disease) is solidly supported by multiple publications (PMID 32445090, 33673725, 25966315, 22770212, 32114424, 32782366). The applications in cancer treatment are moderately supported and clinically limited to specific blood cancers. The anti-ageing applications rest on limited evidence (only PMID 32020082) and are still early-stage experimental.