Epigenetics is the study of how your environment and lifestyle can affect how your genes work without changing the actual DNA sequence. It’s like turning a light switch on or off—your genes can be "switched" on or off depending on factors like diet, stress, or toxins. These changes can influence your health and the way your body functions, but they don’t alter the genetic code itself. One common example of an epigenetic change is DNA methylation (DNAm), where small molecules attach to DNA and change how a gene is expressed. This is the epigenetic modification that we focus on here at TruDiagnostic.
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Dr. Morgan Levine, Vice President of Computation at Altos Labs
https://www.youtube.com/watch?v=B_CqKVU19ec&t=406s
What if we could influence the way our genes behave without altering the DNA itself? This is the central question behind Morgan Levine’s research, where she explores the powerful role of epigenetics in human health. Her work focuses on how epigenetic changes, such as DNA methylation, impact gene activity over time, and how these changes can be used to predict biological age through tools known as epigenetic clocks.
Levine's research reveals that aging, and the related changes in gene expression, don't occur at the same rate for everyone, and this variation can help explain differences in health outcomes. By studying the patterns of epigenetic changes she aims to understand how we might influence these processes to delay the onset of age-related diseases and improve overall health. Rather than seeking to "cure" aging itself, Levine's goal is to use epigenetics to optimize healthspan and reduce the risk of disease as we age.
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Epigenetic biomarkers are specific biological markers derived from analyzing DNA methylation patterns in your genome. Unlike traditional blood-based metrics of your health such as serum levels, which provide a single snapshot in time, epigenetic biomarkers uniquely offer insights into ongoing biological functions by predicting levels of nutrients, metabolites, and other essential biochemical entities.
These epigenetic measurements are based on patterns in your DNA methylation landscape, influenced by both genetic and environmental factors. Epigenetic biomarkers provide a more stable and comprehensive view of your health over time, reflecting long-term exposures and trends rather than short-term fluctuations.
Serum levels represent a direct measurement of substances in your blood at a specific point in time. These levels can vary based on recent meals, exercise, stress, and other transient factors.
In contrast, epigenetic biomarkers are derived from DNA methylation patterns, providing a broader and more consistent indication of health, which isn't as influenced by short-term changes. This makes epigenetic biomarkers especially useful for understanding long-term health trends and risks.
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This study compares traditional CRP (C-reactive protein) testing to DNAmCRP, which uses DNAm patterns as a marker for systemic inflammation. CRP is a widely used biomarker for inflammation and is typically measured through blood tests. However, DNAmCRP is a more advanced method that uses epigenetic markers to estimate CRP levels.
Why is DNAmCRP better?
Epigenetic Insights: DNAmCRP offers insights beyond just current inflammation levels by also reflecting lifestyle factors such as diet, smoking, and stress, which influence methylation patterns. This gives healthcare providers a broader understanding of a patient’s health and risk factors.
Predictive Power: DNAmCRP has shown better predictive ability for certain health outcomes, particularly cognitive impairment, compared to regular CRP tests. This is because DNA methylation reflects both genetic and environmental factors, providing a more comprehensive picture of long-term inflammation and health risks.
Stable and Reflective of Long-Term Health: While CRP levels can fluctuate quickly due to short-term changes (like infection or injury), DNAmCRP reflects more long-term, stable inflammation. This makes it a more reliable indicator for conditions that develop over time, such as metabolic and cardiovascular diseases.
See the table below summarizing the difference between CRP and DNAmCRP:
| Criteria | CRP | DNAmCRP | Winner |
|---|---|---|---|
| Impact of cognitive impairment risk (HR & OR) | No association | More highly correlated than CRP | DNAmCRP |
| Precision (ICC value) | 0.72 | 0.82 | DNAmCRP |
| Ease of collection | Blood draw | Blood draw (but fingerstick) | Tie |
DNAmCRP is superior to regular CRP testing because it integrates both genetic predisposition and environmental exposures over time, offering a more nuanced and stable measure of inflammation and its related health risks.
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A methylation risk score (MRS) is a measure that uses patterns of DNA methylation to estimate the likelihood of a person developing certain health conditions. Methylation patterns can provide insights into how genes are being expressed, and in some cases, these patterns are linked to the risk of developing diseases such as diabetes, cardiovascular disease, or cancer.
The score is calculated by analyzing specific sites in the genome where methylation occurs and comparing them to known methylation patterns associated with particular diseases or health outcomes. By assessing these patterns, a methylation risk score can predict disease risk more accurately than traditional methods, sometimes even before symptoms appear.
Polygenic risk scores (PRS) are based on genetic variations, or single nucleotide polymorphisms (SNPs), and provide a fixed risk score from birth, as your genetic code does not change throughout life.
In contrast, MRS are based on epigenetic changes which can change over time due to environmental and lifestyle factors. This makes methylation scores more dynamic and adaptable, providing a real-time snapshot of gene expression and current health status. Methylation risk scores are considered superior in clinical medicine because they reflect the influence of modifiable factors like diet and stress, offer early detection of disease risk, and can track changes following lifestyle interventions. While PRS provides a lifelong, static risk based on your genetic makeup, MRS offers a flexible and more up-to-date reflection of health risks influenced by both genetics and environment.