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 expanding 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:
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
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
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, 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 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
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
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 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