Epigenetics Explained: What It Is and What It Is Not

What epigenetics is

Epigenetics is the study of how cells control gene activity without changing the DNA sequence. [1] NHGRI describes it as the study of chemical modifications on DNA and the proteins that interact with it, which change how strongly genes are turned on and off. [2] Together these modifications make up the epigenome. It is a field of basic biology. It is not a product, a supplement category or a treatment.

Evidence label used on this page: established (described the same way by national bodies), promising but limited, mixed, insufficient evidence and marketing claim. See How We Label Evidence in Specialty Topics.

The two best-known kinds of mark

• DNA methylation is the attachment of small chemical groups called methyl groups to DNA building blocks. [3]
• Histone modification adds or removes chemical tags on the histone proteins DNA is wrapped around, which affects whether a region of DNA is used. [4]

These marks do not change the DNA sequence. They change the way cells use the DNA's instructions. [4] This is how cells that carry the same genome become different cell types. NHGRI says the pattern of marks varies among individuals, tissues and even cells within a tissue. [5]

What is well established

• Normal cell function depends on it. This regulation helps ensure each cell produces only the proteins it needs. [6]
• Some rare disorders involve imprinting. NHGRI notes that some diseases are caused by abnormal imprinting, in which only the maternal or paternal copy of certain genes is switched on. [7]
• Epigenetic changes occur in disease, including cancer. NHGRI states that cancers are caused by changes in the genome, the epigenome, or both. [8] Label: established as a research finding. It does not mean that an epigenetic test result in a healthy person has a clinical meaning.

What human studies suggest, with limits

Environment and lifestyle. NHGRI says factors such as smoking, diet and infection can prompt chemical responses that often lead to changes in the epigenome. [9] One well-known observational study of the Dutch Hunger Winter of 1944-45 found that people exposed to famine before birth had, six decades later, less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings; the association was specific to exposure around conception. [10] Label: promising but limited. It shows an association in one historical population, not that a modern diet or supplement can reprogram the epigenome. See Environmental and Lifestyle Associations With the Epigenome.

Measuring methylation is harder than it sounds. Blood contains many cell types, each with a different methylation profile. In a re-analysis of five published studies, cell composition explained much of the variability in DNA methylation and was heavily confounded with age. [11] Studies that ignore this can mislead. Label: established as a methodological caution.

Inheritance across generations. NHGRI notes that much of the epigenome is reset when parents pass their genomes to offspring, though under some circumstances certain marks may be passed on. [12] In humans, transgenerational epigenetic inheritance remains the subject of controversial debate because it is confounded by genetic, ecological and cultural inheritance. [13] Label: insufficient evidence for claims that lifestyle choices are inherited through the epigenome in people.

Hype and where claims go wrong

A 2019 review in Nature described epigenetic research as producing justified excitement and hope, but also a degree of hype. [14] Be cautious with:

• "Reprogram your genes" or "reset your epigenome" supplement and wellness claims, which are a marketing claim unless a human trial measured a clinical outcome.
• Treating a change in a methylation marker as a health benefit. A biomarker change is not a clinical outcome. See Biomarkers vs Clinical Outcomes.

Consumer epigenetic tests are covered in Epigenetic Wellness Tests, and how they differ from DNA sequence tests in Genetic Testing vs Epigenetic Testing.

Aging clocks belong to Longevity

Methylation-based "biological age" estimates are evaluated in the Longevity library. See Epigenetic Clocks and DNA Methylation in Aging and Biological Age Clocks Compared. This page does not rate them.