Scientific Resources

The Science of Epigenetics

Epigenetics is changing our understanding of biology and emerges as a response to many unexplained consequences of disease development. This new science demonstrates that our environment and lifestyle influence the behavior of our genes and explores why the information in our genes is not sufficient to explain the complex patterns linked to health issues.

As scientists, evidence is at the core of our work, therefore we approach the epigenetic revolution based on existing data and we are excited to participate in new potential advances in this field.

We are happy to offer a short insight on the explosion of scientific literature in the fastest-growing research areas in biology.

WHAT IS EPIGENETICS?

The epigenome (literally “above the genome”) represents every heritable modification added on top of the genome without affecting the sequence of letters (A; T; C or G) that make up our DNA. More precisely, the addition or removal of methylated groups (-CH3) at specific sites in the genome modulates the expression of our genes. Appropriate regulation of gene expression is essential to the proper functioning of the human body. As an example all our cells have the same DNA sequence but each cell has a different shape and function, modulated by epigenetics.

Misregulation can lead to diseases. Regulation of epigenetic mechanisms is very complex and relies on genetic and environmental factors. While DNA is almost immutable, the epigenome is modulable through specific actions.

Advances in epigenetics link genetics to the environment and disease.
Review on the evolving field of epigenetics and its recent advances
Cavalli & Co – Nature – 2019

DNA methylation dynamics in health and disease
Dynamics of DNA methylation during development and abnormal methylation changes that occurs in cancer
Bergman & Co – Nature Structural & Mol. Biol. – 2013

EPIGENETICS & AGEING

Ageing is the gradual deterioration of physiological function. The causes of ageing, induced by complex mechanisms, are largely debated. As most biological processes, aging has both internal genetic components (different species have a similar lifespan and rare genetic diseases can trigger premature aging) and external components (e.g. calorie restriction can extend lifespan in several species).

Though it is widely believed that long life runs in families for genetic reasons, estimates of the genetic part of ageing are consistently well below 20%. There is indeed a strong environmental component in aging. For example, sun exposure may accelerate skin aging due to the accumulation of damages over time.

While ageing is a multifactorial process, accumulating evidence links aging to epigenetic alterations. Given the reversible nature of epigenetic mechanisms, these pathways provide promising avenues for therapeutics against age-related decline and disease.

For more information:

The genetics of human ageing
A review of large-scale genome-wide association studies that identified many loci that influence key human ageing traits, including lifespan.
Melzer & Co – Nature reviews Genetics – 2020

Aging Genetics and Aging
A review on the best-known genetic factors involved in aging.
Rodríguez-Rodero & Co- Aging and Disease – 2011

BIOLOGICAL AGE, A MEANINGFUL MEASURE

Recent research sheds light on how aging can be impacted by external factors, including diet, exercise, stress, environment and smoking. Many gerontologists believe chronological age to be an incomplete figure because it doesn’t take these external factors into consideration.

Interestingly, organisms of the same species age at different rates, demonstrating the reality of biological ageing as opposed to chronological ageing.

Biological age or Epigenetic age is a measurement of your age based on the combination of various methylation biomarkers. In other words, Biological age is a scientific estimate of the physiological state of individuals. It encompasses longevity and the ability to function (healthy aging) and takes many factors into consideration, time, genetics, but also lifestyle including diet, exercise and sleeping habits, to name a few.

For more information:

Patterns of DNA methylation as an indicator of biological aging: State of the science and future directions in precision health promotion
A literature review surrounding epigenetic age estimated by DNA methylation.
Shannon & Co – Nursing Outlook – 2019

An epigenetic biomarker of aging for lifespan and healthspan
A new epigenetic biomarker of aging, that strongly outperforms previous measures in regard to predictions for a variety of aging outcomes.
Levine & Co – Aging (Albany NY) – 2018 

DNA methylation GrimAge strongly predicts lifespan and healthspan
A composite biomarker based on epigenetic markers to predict lifespan and health span of humans.
Lu and Co – Aging (Albany NY) – 2019 

Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates
A quantitative model of the aging methylome that demonstrates high accuracy and ability to discriminate relevant factors in aging, including gender and genetic variants.
Gregory Hannum & Co – Molecular cell – 2013

DNA methylation age of human tissues and cell types
DNA methylation age measures the cumulative effect of an epigenetic maintenance system.
Steve Horvath – Genome Biology – 2013

DNA methylation-based biomarkers and the epigenetic clock theory of ageing
“Epigenetic clocks” link the processes of development and maintenance to biological aging and give birth to a unified theory of the course of life.
Steve Horvath & Co – Nature Reviews Genetics – 2018

Biological Versus Chronological Aging
Current knowledge on biological age biomarkers, factors influencing it, and antiaging interventions, with a focus on vascular aspects and its cardiovascular disease related manifestations.
Horvath & Co – Nature Review Genetics 2018

LIFESTYLE AND ENVIRONMENTAL FACTORS IMPACT OUR EPIGENETIC

We are constantly exposed to a multitude of stresses, compounds and to diverse environments. In the last few years, an increasing number of studies have examined the relation between epigenetic markers and lifestyle factors, including nutrition, behavior, stress, physical activity, working habits, smoking or alcohol consumption. As our body faces its environment, we react by fine-tuning the expression of our genes, for example as we expose ourselves to sunlight, we produce more melanin, which is triggered by an activation of several genes. This genetic modulation is controlled by epigenetic mechanisms.

At genknowme, we can measure those mechanisms and quantify the impacts of lifestyle choices. We cannot change our genome or stop the passage of time. However we can influence our genes by making better life choices and follow the impact of those changes by measuring our epigenetic.

For more information, here are some scientific articles:

Epigenetics and lifestyle
Evidence indicating that lifestyle factors might affect human health via epigenetic mechanisms.
Alegria-Torres & Co – Epigenetics – 2013

And more specifically per lifestyle factors:

Alcohol

A DNA methylation biomarker of alcohol consumption
A robust alcohol related methylation signature useful to detect heavy alcohol consumption.
Liu & Co – Molecular Psychiatry – 2018

DNA methylation age is accelerated in alcohol dependence
Epigenetic aging differs in blood and liver tissue of individuals with alcohol dependance compared to healthy volunteers.
Rosen & Co – Translational psychiatry – 2018

Tobacco

Current and Future Prospects for Epigenetic Biomarkers of Substance Use Disorders
Recent progress in assessment of substance abuse through epigenetics.
Andersen & Co – Genes – 2015

Epigenetic Signatures of Cigarette Smoking
New sites differentially methylated in relation to smoking habits that persist long after smoking cessation.
Joehanes & Co – Circ. Cardiovasc. Genet. – 2017

Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation
Dynamic of epigenetic changes in response to cigarette smoking and cessation.
Tsaprouni & Co- Epigenetics – 2014

Nutrition

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways
Fruit and juice consumption influence different immune cell populations and different aspects of immune function.
Nicodemus-Johnson & Co – Nutrients- 2017

The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition
An investigation on the impacts of exercise and nutrition on cardiovascular health.
Wallace & Co- Mech. Of Ageing and Dev. – 2018

Physical Activity

Physical Activity, Television Viewing Time, and DNA Methylation in Peripheral Blood
DNA methylation may be a biological mechanism linking physical activity and sedentary behavior to chronic disease development.
Roekel & Co – Epidemiology – 2019

Physical Activity and Genome-wide DNA Methylation: The REgistre GIroní del COR Study
Two new CpGs of interests associated with moderate vigorous activity.
Fernandez-Sanlés & Co – Med Sci Sports Exerc. – 2020

Precision Physical Therapy: Exercise, the Epigenome, and the Heritability of Environmentally Modified Traits
Emerging knowledge supporting epigenetic adaptation to exercise in human.
Woelfel & Co – Physical Therapy – 2018

Accelerometer-measured Physical Activity, Reproductive Hormones, and DNA Methylation
Physical activity lowered the methylation of growth-related gene in teenage boys.
Wu & Co – Med Sci Sports Exerc. – 2020

BIOLOGICAL AGE IS LINKED TO ALL-CAUSE MORTALITY

Only a small number of studies investigated the association between DNA methylation and age-related disease and longevity. However, even though there is a need for more research, the scientific literature seems to acknowledge that epigenetic markers of ageing can predict the incidence of common disease and all-cause mortality.

For more information:

Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up
Biological Age has the potential to provide mortality-relevant information independently of Chronological Age.
Liu & Co, eLife – 2020

The Epigenetic Clock as a Predictor of Disease and Mortality Risk: A Systematic Review and Meta-Analysis
Systematic review to identify and synthesize the evidence for an association between DNAmAge and longevity, age-related disease, and mortality risk.
Fransquet & Co – Clin Epigenetics – 2019

Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden
Epigenetic markers of ageing predict incidence of common disease.
Hillary & Co – BioRxiv – 2020

DNA Methylation-Based Measures of Biological Age: Meta-Analysis Predicting Time to Death
Gene methylation are like other complex traits: influenced by both genetic and environmental factors and associated with major health-related outcomes.
Marioni & Co – Genome Biol – 2015

Association of DNA Methylation-Based Biological Age With Health Risk Factors and Overall and Cause-Specific Mortality
Age acceleration measures are associated with several established health risk factors and with mortality.
Dugué & Co – American J. of Epidemiology – 2018

 

More scientific papers on the subject:

Frailty, fitness and late-life mortality in relation to chronological and biological age

DNA methylation age of blood predicts all-cause mortality in later life

DNA Methylation Age Is Associated With Mortality in a Longitudinal Danish Twin Study

Decreased Epigenetic Age of PBMCs From Italian Semi-Supercentenarians and Their Offspring

EPIGENETIC’S OPPORTUNITIES AND APPLIED POTENTIALS

Over the past five years, several groundbreaking scientific publications have demonstrated a link between epigenetic markers and environmental factors, lifestyle and disease. To name just a few: stress, smoking, diet, mental health, physical activity, immune response and various diseases such as cancer have shown an epigenetic component. This list highlights the enormous potential of epigenetics and although research in this field still needs to be expanded to obtain more validations, the applications seem extremely broad. It includes not only diagnostic opportunities but also high prognosis opportunities that could potentially change preventive medicine.

Here is a selection of publications illustrating the enormous field of application of epigenetic:

The quest to slow ageing through drug discovery
A review on the most promising interventions to slow ageing
Partridge & Co – Nature Reviews Drug Discovery – 2020

First hint that body’s ‘biological age’ can be reversed
Body’s epigenetic clock reversed for 9 volunteers who took a cocktail of three common drugs during one year.
Abott – Nature – 2019

Reversal of epigenetic aging and immunosenescence trends in  humans
Regression of epigenetic age after a treatment intended to regenerate the thymus
Fahy & Co – Aging Cell – 2019

Effects of Vitamin D 3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status
Vitamin D supplementation may slow down Horvath epigenetic aging
CHen & Co – J. of Gerontology – 2019

Dietary Intervention Modifies DNA Methylation Age Assessed by the Epig. Clock
Supplementation with folic acid + vit B12 modulate global DNA methylation profiles.
Sae-Lee & Co – Molecular Nutrition – 2019

The Impact of Caloric Restriction on the Epigenetic Signatures of Aging
Review on the current knowledge on the impact of caloric restriction on the epigenetic signatures of aging.
Gensous & Co- Int. J. of Molecular Science – 2019

Cancer

Cancer is generally explained by a dysfunction of cellular internal regulation (ie. proliferation), which are mechanisms that can be mediated by epigenetic mechanisms. There is plenty of evidence that genetic signatures can be linked to cancer development prediction.

Epigenetic Changes Could Signal Increased Cancer Risk

Epigenetic drift, epigenetic clocks and cancer risk | Epigenomics

Methylation-Based Biological Age and Breast Cancer Risk

Increased Epigenetic Age in Normal Breast Tissue From Luminal Breast Cancer Patients

Epigenome-wide association studies for breast cancer risk and risk factors

Epigenetic targeting in lymphoma – Booth – – British Journal of Haematology

EAU 2020: Urinary Markers in Low-Grade Non-Muscle Invasive Bladder Cancer: Ready to Stop Cystoscopies

Mental health

The Epigenetics of Stress

Epigenetic Aging in Major Depressive Disorder

Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation

Poor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional interventions

Traumatic Stress and Accelerated Cellular Aging: From Epigenetics to Cardiometabolic Disease

Accelerating research on biological aging and mental health: Current challenges and future directions

Pilot study of DNA methylation, molecular aging markers and measures of health and well-being in aging

Transgenerational effects

The far-reaching effects of antidepressants

Transgenerational Hypocortisolism and Behavioral Disruption Are Induced by the Antidepressant Fluoxetine in Male Zebrafish Danio rerio

Intergenerational transmission of the positive effects of physical exercise on brain and cognition

Alcohol effects on the epigenome in the germline: role in the inheritance of alcohol-related pathology

Epigenetics and drug response

Epigenetics in Drug Response

Epigenetics and health

The diverse roles of DNA methylation in mammalian development and disease

Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease

Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations

Epigenetic Age Acceleration: A Biological Doomsday Clock for Cardiovascular Disease?

Epigenetic and immune response

The emerging role of epigenetics in the immune response to vaccination and infection: a systematic review

Epigenetic Dysregulation of ACE2 and Interferon-Regulated Genes Might Suggest Increased COVID-19 Susceptibility and Severity in Lupus Patients

MERS-CoV and H5N1 Influenza Virus Antagonize Antigen Presentation by Altering the Epigenetic Landscape

Epigenetic Landscape During Coronavirus Infection

Epigenetic mechanisms regulating COVID-19 infection

Epigenetic and  meditation

Study reveals gene expression changes with meditation