Everything Epigenetics - The Importance of the Imprintome with Dr. Randy Jirtle

The Importance of the Imprintome with Dr. Randy Jirtle

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.

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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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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.

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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

Support the show

Where to Find Us:
Instagram

Visit our website for more information and resources: everythingepigenetics.com

Previous Episode

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

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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Where to Find Us:
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Visit our website for more information and resources: everythingepigenetics.com

Next Episode

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

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.

Support the show

Where to Find Us:
Instagram

Visit our website for more information and resources: everythingepigenetics.com