Everything Epigenetics

Hannah Went

Don’t understand epigenetics? Don’t worry. There was a time when genetic analysis was hardly known or understood. Now, genetic analysis is performed by thousands of companies and your full genome can be decoded for less than $100. Epigenetics is how your behaviors change your outcome. Epigenetics gives us knowledge on how to change your life, and the ability to read biology to understand your current health status. You ARE in control. Your host, Hannah Went, is here to discuss the insights which can improve your life and health. She is here to bring you Everything Epigenetics, simplified.

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Top 10 Everything Epigenetics Episodes

Goodpods has curated a list of the 10 best Everything Epigenetics episodes, ranked by the number of listens and likes each episode have garnered from our listeners. If you are listening to Everything Epigenetics for the first time, there's no better place to start than with one of these standout episodes. If you are a fan of the show, vote for your favorite Everything Epigenetics episode by adding your comments to the episode page.

Epigenetic Gestational Age Prediction with Kristine Løkås Haftorn

Everything Epigenetics

02/07/24 • 56 min

Determining a newborn's due date traditionally relies on maternal reports of the last menstrual period and ultrasound scans.
These conventional approaches can lead to uncertainties, especially when it comes to identifying deviations from normal fetal development that could impact research into the effects of preterm or post-term births on newborns.
However, researchers, including Kristine Løkås Haftorn, have now developed a more precise method to ascertain newborns' gestational age through analyzing DNA methylation patterns in blood samples, utilizing machine learning.
This is crucial because accurate knowledge of gestational age is fundamental for understanding the risks and implications of preterm and post-term births on infant health.
Moreover, the ability to accurately determine gestational age in utero could revolutionize prenatal care by providing deeper insights into fetal development, potentially allowing for earlier identification of developmental issues and more tailored interventions to support healthy pregnancies.
This breakthrough, driven by machine learning's ability to sift through and interpret complex epigenetic information, underscores the potential of combining technology with biology to enhance our understanding of human development.
In this week’s Everything Epigenetics podcast, I speak with Kristine about epigenetic gestational age prediction, how we can use gestational age clocks to look at developmental timing and how this can improve pregnancies, assisted reproductive technology (ART), and more.
Kristine is particularly interested in epigenetic patterns in newborns, how these patterns are linked to development in the fetus and child, and how they can be affected by various exposures during pregnancy.
In this Everything Epigenetics episode, you’ll learn about:

DNA methylation's role in fetal development
Gestational age and how is it linked to fetal development
Predicting gestational age using epigenetics
Why determining specific cell types responsible for an association between DNA methylation and a given phenotype important
How Kristine is adjusting for cell type composition in her work
What cell-type specific DNA methylation patterns are associated with gestational age
Nucleated red blood cells
Why Kristine believes nucleated red blood cells are the main cell type driving the DNAm-GA association
The poor correlation observed between epigenetic age clocks for newborns and those for adults
How we can use gestational age clocks to look at developmental timing and how this can improve pregnancies
Assisted reproductive technology (ART)
Differences in disease in ART babies and traditional birth babies
Epigenome-wide association studies of ART
Investigating CpGs on the X chromosome

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Thank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how to harness this knowledge for your benefit.

Causal Epigenetic Age Uncouples Damage and Adaptation with Kejun (Albert) Ying

Everything Epigenetics

01/24/24 • 46 min

Machine learning models that use DNA markers can estimate the age of biological samples. However, understanding why these markers change with age is challenging because it's hard to prove that these changes cause aging-related traits.
In this week’s Everything Epigenetics podcast, I speak with Kejun Ying who uses large datasets to find specific DNA markers that directly influence aging traits.
We explore his recently published study which found casual CpGs that speed up aging and others that protect against it.
Kejun and colleagues created two new models, DamAge and AdaptAge, to measure harmful and beneficial changes related to aging. DamAge, which indicates negative aging effects, is linked to several health risks, including higher chances of dying. AdaptAge, on the other hand, shows positive aging adaptations. Interestingly, only the negative changes seen in DamAge can be reversed by a process that makes aged cells young again.
The research findings provide a detailed understanding of the DNA markers that truly affect lifespan and overall health as we age. This helps us develop more accurate aging biomarkers and evaluate treatments aimed at reversing aging, improving longevity, and understanding events that speed up the aging process.
In this Everything Epigenetics episode, you’ll learn about:

Kejun’s unique journey into the aging field
One of the biggest weaknesses of the epigenetic clocks (separating causation versus correlation)
Mendelian randomization
Casual inference
Why causality matters for aging biomarkers
Why it is important to separate deleterious and protective changes in aging
DamAge (casual aging clock based on damaging sites)
AdpateAge (casual aging clock based on protective sites)
The applications of DamAge and what AdpateAge
ClockBase: a comprehensive platform for biological age profiling in human and mouse
The application of ClockBase
Data privacy when using ClockBase

Where to find Kejun:

Kejun Ying is a 4th year Ph.D. student in Harvard Medical School, Gladyshev lab. His research focuses on understanding cause of aging and develop ML-based aging biomarkers to facilitate the discovery of novel anti-aging interventions.

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The Importance of the Imprintome with Dr. Randy Jirtle

Everything Epigenetics

01/10/24 • 54 min

The idea of the impintome is still foreign to many people. So, let’s start with a simple explanation.
For the majority of genes, we inherit two functional copies—one from our mother and one from our father. However, imprinted genes follow a different pattern, as we inherit only one functional copy. Depending on the specific gene, either the copy from our mother or our father undergoes epigenetic silencing. This silencing process typically involves the addition of methyl groups during the formation of eggs or sperm.
The epigenetic modifications on imprinted genes typically stay put throughout the organism's lifespan but undergo a reset during the formation of eggs and sperm. Regardless of their origin, certain genes are consistently silenced in eggs, while others are consistently silenced in sperm.
Soon after egg and sperm meet, most of the epigenetic tags that activate and silence genes are stripped from the DNA. However, in mammals, imprinted genes keep their epigenetic tags. Imprinted genes begin the process of development with epigenetic tags in place.
Imprinted genes are not the only genes that bypass epigenetic reprogramming in the early embryo. Studying imprinting may help researchers understand how other genes make it through reprogramming without losing their epigenetic tags.

–

The field of epigenetics and the imprintome has grown exponentially in the past decade, largely fueled by Randy Jirtle's groundbreaking research.
Picture this: his 2003 study on how nutrition impacts gene regulation is the single most talked-about paper in the history of science. Jirtle's discoveries have been a game-changer, unraveling secrets about human health and the roots of diseases.
In this week's Everything Epigenetics podcast, I dive into a captivating conversation with Dr. Jirtle. We explore the fascinating intricacies of his research, unravel its profound implications for understanding disease development, and uncover the urgent call for more scientists to embark on the mesmerizing journey into the world of epigenetics.

In this Everything Epigenetics episode, you’ll learn about:

Jirtle’s seminal 2003 Agouti mouse study
The concept of imprinting and epigenetics
The evolutionary biology approach
How environmental and nutritional exposures can determine phenotypes through epigenetic regulation
The profound impact that Jirtle had on the scientific community with his research
How to identify imprintome regulatory regions in the germline
The discovery of the full imprintome control regions in July 2022
How to measure the imprintome with the imprintome array
How the imprintome is starting to connect the dots to certain disease risks
Future research on imprtinting and human evolution
Challenges in researching the imprintome
Pragmatic appl

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Integrating Epigenetics into the Social Models of Heath Disparities with Dr. Lauren Schmitz

Everything Epigenetics

12/27/23 • 52 min

Did you know that the Great Depression—the worst economic downturn in US history—impacted how fast individuals aged biologically decades later according to their epigenetic aging profiles?!
Yep... you read that right.
Results show that faster epigenetic aging later in life is associated with worse economic conditions, specifically, during the prenatal period, suggesting it may be a sensitive window for the development of later-life disparities in aging. As a result, early-life investments may help postpone age-related morbidity and mortality.
In this week’s Everything Epigenetics podcast, Dr. Lauren Schmitz speaks with me about just that. We take a deep dive into several of her studies which focuses on using genetic and epigenetic measures alongside data on the social environment from population-based longitudinal studies and randomized control trials.
Lauren and I also discuss the methodology she uses for uncovering causal effects from observational data, with the ultimate goal of identifying policy targets that enhance quality of life and extend healthspan.
We also chat about her study results that support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these World Health Organization (WHO) risk factors, as well as, social disadvantages which may contribute additively to faster biological aging.
I’m extremely excited and passionate about Lauren’s work myself, as it suggests that epigenetic aging measures may contain additional valuable information that could further our understanding of the causes of social disparities in aging and health span.
Lauren is now actively working on assessing measures of biological age in a low-income context, specifically “The Malawi Longitudinal Study of Families and Health”.
In this Everything Epigenetics episode, you’ll learn about:

Lauren’s atypical, windy road into science
The Health and Retirement study
Maternal-fetal epigenetic programming
Why it’s important to look at early-life exposures to adverse events
How we can look at early-life exposures to adverse events through the lens of Epigenetics
In utero exposure to the Great Depression being reflected in late-life epigenetic aging signatures
How early-life investments may help postpone age-related morbidity and mortality and extend healthy life span
Lauren’s study “The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study”
Another one of Lauren’s study titled: “The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis”
Why is it important to conduct research on the connection

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Unlocking the Epigenome from a Single Drop of Blood with Dr. Toinét Cronjé

Everything Epigenetics

11/29/23 • 49 min

In this week’s Everything Epigenetics episode, I speak with Dr. Toinét Cronjé about what epigenetics can do for the field of epidemiology.
Epidemiology is the study of the distribution and determinants of health-related states or events in populations and the application of this study to control health problems. By studying epigenetics and epidemiology in tandem, Dr. Cronjé seeks to understand patterns of diseases in populations, identify risk factors, and develop strategies to prevent or control health issues.
More specifically, Dr. Conjé researches epigenetics in understudied populations including the association between DNA methylation and noncommunicable diseases and how DNA methylation clocks perform in these groups.
By making the most of the data we have available at the moment (from high-income countries) and of opportunities provided to researchers like herself to work at leading universities like the University of Copenhagen, she hopes that we will get closer to finding the tools to ease the burden on the research communities in low and middle income countries (LMICs).
If we can truly start to investigate data from LMICs can you imagine the richness of the information we will unearth?
Many of the questions that we are struggling with will be easier to address if we have more diversity in research data sets (e.g. genetics, cultural, dietary, and environmental), as rich (diverse) data sets allow researchers to see more angles to approach their questions from that they might not have been able to see before.
Dr. Cronjé’s hope is to develop blood-based screening tools for a disease. Only then, when disease screening is accessible to all (e.g. through a blood test instead of intensive and invasive procedures) will we actually know what proportion of populations around the world actually suffer from diseases like these.
Using that as a starting block we can finally proceed to addressing stigma and improving care.

In this episode of Everything Epigenetics, you’ll learn about:

Toinét’s unique background
OMIC epidemiology
What epigenetics does for epidemiology
The importance of biobanks
What we can tell you about yourself when investigating the epigenome using an archived sample from a biobank
Why it’s important to research understudied populations
What we can learn from low and middle income countries
What the research community is missing out on by not studying these groups
Noncommunicable diseases (NCDs)
The association between DNA methylation and NCDs
The urban-rural divide which provides a unique opportunity to investigate the effect of the combined presence of multiple forms of environmental exposure on DNAm and the related increase in disease risk
Toinét’s study on “Comparison of DNA methylation clocks in black Sout

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Methylation Risk Scores with Dr. Mike Thompson

Everything Epigenetics

11/01/23 • 62 min

You may be familiar with polygenic risk scores (PRS), but have you ever heard of methylation risk scores (MRS)?
MRS are crucial to understand, as they’re a tool that quantifies DNA methylation levels at specific genomic regions linked to particular conditions, shedding light on the potential impact of epigenetic modifications on disease susceptibility.
In contrast, PRS calculates an individual's genetic disease risk by considering multiple genetic variants across the genome, often identified through genome-wide association studies.
While PRS offers valuable insights into genetic predisposition for complex diseases such as heart disease and diabetes, it has its limitations, including the risk of false positives and challenges in clinical interpretation.
The choice between MRS and PRS depends on the specific disease or research context and the available data, as both scores provide unique perspectives on disease risk.
In this week’s Everything Epigenetics podcast, Dr. Michael Thompson and I chat about the importance and benefits of MRS, how to calculate such scores, and how these scores compare to PRS. For example, in his recent paper, Mike discovered that MRS significantly improved the imputation of 139 outcomes, whereas the PRS improved only 22.
We focus on the results from a study Mike published last year that showed MRS are associated with a collection of phenotypes with electric health record systems. Mike’s work added significant MRS to state-of-the-art EHR imputation methods that leverage the entire set of medical records, and found that including MRS as a medical feature in the algorithm significantly improves EHR imputation in 37% of lab tests examined (median R2 increase 47.6%). His publicly available results show promise for methylation risk scores as clinical and scientific tools.
Mike is currently in Barcelona working on using artificial intelligence to map and learn the biological effects of mutating everything (and anything) in every single position from a genetic variant to the change in splicing or to some other interesting phenotype.
In this episode of Everything Epigenetics, you’ll learn about:

How Mike got into the field of Epigenetics
What epigenetics means to Mike
Mike’s interesting background starting with his undergraduate journey to his graduate and postgraduate studies
The importance and limitations of electric health records (EHR)
The importance and benefits of methylation risk scores (MRS)
The importance and limitations of polygenic risk scores (PRS)
How MRS compares to polygenic risk scores
Mike’s paper titled “Methylation risk scores are associated with a collection of phenotypes within electronic health record systems” and what prompted this investigation
How you create an MRS
Why we don’t see MR

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A Deeper Dive into DunedinPACE with Dr. Daniel Belsky

Everything Epigenetics

07/19/23 • 52 min

According to Dr. Daniel Belsky at Columbia University, there are three limitations of epigenetic biological age clocks:

1. Mortality selection

Essentially, biological age measures may underestimate true aging because older participants represent slower agers.
2. Cohort Effects

Biological age measures may overestimate true aging because older participants carry an excess burden of early-life exposure to environmental toxicants, pathogens, poor nutrition, smoking, etc.
3. Uncertain Timing
Biological age measures summarize total aging over the lifespan and cannot distinguish differences established early in development from ongoing processes of aging. As a result, biological clocks may have lower sensitivity to effects of intervention.

So, you’re probably wondering, how do we account for these limitations?
Dr. Belsky and his team have created a tool that enhances the precision of measuring the rate of biological aging. Their work involved observing the health outcomes of 954 participants across four different age groups spanning from the mid-20s to the mid-40s. The researchers examined biomarkers believed to indicate how well various organs are functioning, as well as others linked to general health. Using this data, they devised an epigenetic "speedometer" to forecast how these values would change over time.
This tool is called the DunedinPACE.
As you may already know, the DunedinPACE measures how fast you are aging biologically for every one chronological year. If you need an introduction to DunedinPACE, check out my episode with Dr. Terrie Moffitt HERE.
In this week’s Everything Epigenetics podcast, Dan Belsky and I take a deeper dive into why Biological Age is limited and how DunedinPACE overcomes these limitations. Dr. Belsky speaks with me about a geroscience model of aging-related burden of disease, DunedinPACE test-retest reliability, and why the DunedinPACE indicates a faster pace of aging in individuals with an older chronological age.
We also discuss the effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.
The DunedinPACE is a new tool for geoscience to investigate etiology in epidemiological studies and to evaluate the treatment effects of randomized controlled trials.
Dr. Belsky continues to validate the DunedinPACE in other populations around the world.
In this episode of Everything Epigenetics, you’ll learn about:

Dan Belsky’s unusual journey into aging science
How to measure aging in younger people
A geroscience model of aging-related burden of disease
Why it’s important to have such model
Clinical trials which

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How Fit Are You According to Your DNA? With Kristen McGreevy

Everything Epigenetics

07/05/23 • 49 min

As we age, physical fitness tends to decline. This decline can be attributed to various factors such as changes in body composition, reduced muscle mass and strength, decreased flexibility, and diminished cardiovascular endurance. Additionally, the body's ability to recover from physical exertion also tends to slow down with age.
It has been well validated that the rate at which this decline occurs varies among individuals. However, those who maintain their physical fitness as they age experience a lower risk of various diseases and tend to enjoy longer lives.
At the molecular level, changes in fitness and related indicators of functional capacity coincide with molecular markers of decline, which are believed to reflect underlying biological aging processes. Therefore, measurements of fitness offer a novel perspective on biological aging.
Nevertheless, the measurement of fitness parameters presents challenges due to the need for in-person data collection by skilled experts utilizing specialized equipment. Moreover, remote data collection or studies involving stored biospecimens do not facilitate direct assessments of fitness.
To overcome this limitation and facilitate the evaluation of fitness in such scenarios, Kristen Mcgreevy has developed blood-based DNAm biomarkers that encompass various aspects of fitness, including mobility (gait speed), strength (grip strength), lung function (forced expiratory volume in one second), and cardiovascular fitness (VO2 max). These biomarkers form the basis of a groundbreaking indicator known as DNAmFitAge, which quantifies biological age based on fitness levels. This research also highlights the influence lifestyle has on the aging methylome.
In this week’s Everything Epigenetics podcast, Kristen and I chat about the importance of physical fitness as we age, how she developed blood DNAm biomarkers for four fitness parameters, and how she created DNAmFitAge. We also focus on FitAgeAcceleration in age-related conditions and DNAmFitAge relationship to physical activity and body builders.
Kristen is in the final year of her PhD, studying biostatistics at UCLA.
In this episode of Everything Epigenetics, you’ll learn about:

Kristen McGreevy’s interest in biostatistics and epigenetics
Why Kristen made the decision to get her PhD
The definition of strength training
Why physical fitness is important for aging
Which aspect of physical activity is the most important for longevity and health
What prompted Kristen to create DNAm estimators of fitness parameters
Gait speed (walking speed)
Handgrip strength
Forced expiratory volume in 1 second (FEV1; an index of lung function)
Maximal oxygen uptake (VO2max; a measure of cardiorespiratory fitness
Why Kristen chose gait speed, grip strength, FEV1, and VO2max for h

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Predicting Mental Illnesses Using Epigenetics with Dr. Zachary Kaminsky

Everything Epigenetics

06/21/23 • 50 min

According to the National Institute of Mental Health, approximately 20% of adults (around 51.5 million people) experience a mental illness each year. I believe that is 51.5 million people too many!
There is a HUGE need for the ability to predict mental illness, as the current diagnostic process has many limitations and challenges.
By analyzing epigenetic markers associated with mental disorders, we can actually predict the likelihood of developing these conditions and tailor personalized treatment plans for improved outcomes.
Predicting mental illness using epigenetics is paramount for early intervention, personalized medicine, and improved outcomes. With DNA methylation marks in peripheral tissues serving as predictive biomarkers, healthcare professionals can identify those at high risk and initiate targeted support.
Early detection enables timely interventions, potentially mitigating the severity and progression of these disorders. By leveraging cutting-edge technologies like artificial intelligence and natural language processing, we can even analyze social media data to predict suicidal thoughts and behaviors, revolutionizing suicide prevention strategies.
In this week’s Everything Epigenetics podcast, Zach and I chat about his work which primarily concentrates on identifying the epigenetic factors that contribute to psychiatric diseases, specifically focusing on mood disorders.
We discuss the microarray technology he utilizes to conduct genome-wide exploratory analyses, aiming to discover disease associations in both human subjects and animal models. We focus on Zach’s investigations which encompass a range of conditions, including major depression, postpartum depression, and suicide.
Another significant area of Zach’s research that we explore is centered around the development of predictive biomarkers for disease risk, using DNA methylation patterns in peripheral tissues.
Furthermore, we talk about his research program that involves the development and application of artificial intelligence-driven natural language processing techniques, and how he applies these techniques to social media data to predict the likelihood of future suicidal thoughts and behaviors.
Additionally, Zach is focused on creating and evaluating innovative digitally delivered suicide interventions that make use of these technologies.

In this episode of Everything Epigenetics, you’ll learn about:

Zach’s story starting with, “I met a girl...”
Zach’s focus on suicide, PTSD, and post-partum depression epigenetics
Dionysus digital health
Why epigenetics is giving researchers hope as a diagnostic tool
Epigenetics being the common denominator of nature and nurture
Stress vulnerability and epigenetic variation
The importance of replication and validation studies
Mol

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From Aging to Cancer Risk in Epigenetics with Dr. Chiara Herzog

Everything Epigenetics

10/23/24 • 48 min

In this week's episode of the Everything Epigenetics podcast, Dr. Chiara Herzog and I talk about how epigenetics is making waves in the medical world and how it could change treatment. Translational scientist and research fellow Dr. Herzog provides insights from her role in the Biomarkers of Aging Consortium and her work on the TirolGESUND project, one of the largest multi-omic human lifestyle intervention trials to date. We investigate the potential applications of epigenetics in cancer detection, aging biomarkers, and preventive measures that could change the paradigm of healthcare from one that is reactive to one that is proactive. We also explore the fascinating potential of using epigenetic markers to anticipate disease before it manifests itself, particularly in the context of cancer research, and how this could impact the delivery of tailored healthcare.

You'll learn about:

How Dr. Herzog’s background in neuroscience led her to epigenetics
Recent breakthroughs in epigenetics and why they are promising for healthcare
The potential of epigenetic markers to predict cancer risk and diagnose early stages of cancer
The setup and goals of the TirolGESUND study focusing on intermittent fasting and smoking cessation
The importance of studying epigenetic changes across different cell types and understanding the exposome
How the exposome interacts with our epigenome and its implications for personalized medicine

Chapters:
00:00 Welcome and introduction
02:30 Dr. Herzog’s journey from neuroscience to epigenetics
05:40 Recent breakthroughs in epigenetic research
12:10 Epigenetics and cancer risk: promising findings
19:15 TirolGESUND study: setup, interventions, and what to expect
27:40 Why studying different cell types matters in epigenetics
32:00 Understanding the exposome and its impact on health
38:20 Future steps for advancing epigenetic biomarkers in healthcare
45:00 Exciting upcoming projects in epigenetics research

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