Morgan Levine, PhD, on PhenoAge and the Epigenetics of Age Acceleration — can we change the pace?
FoundMyFitnessKey Moments
Epigenetic clocks reveal biological age, predicting health and mortality. Interventions and lifestyle may influence this "age."
Key Insights
Chronological age differs from biological aging, which reflects molecular and cellular changes affecting health and function.
Epigenetic clocks, particularly DNA methylation patterns, serve as powerful biomarkers for estimating biological age across tissues.
Second-generation epigenetic clocks (e.g., PhenoAge, GrimAge) are more predictive of health outcomes like mortality than first-generation clocks.
Epigenetic age acceleration (predicted age > chronological age) is linked to lifestyle, environmental factors, and health status, with genetics playing a minor role.
Partial cellular reprogramming shows promise in reversing epigenetic age and hallmarks of aging, though human applications are still in early stages.
Plasma exchange and interventions like diet and exercise can influence epigenetic age, highlighting the plasticity of biological aging.
DIFFERENTIATING CHRONOLOGICAL VS. BIOLOGICAL AGE
The conversation begins by distinguishing between chronological age (the number of years lived) and biological or phenotypic aging, which encompasses the actual physical and functional changes a body undergoes over time. While chronological age is a simple count, biological aging refers to how a body's molecular and cellular structures have changed, impacting disease risk and functional capacity. Scientists are most interested in biological aging because it's considered more fundamental and represents where interventions might be most effective.
EPIGENETIC CLOCKS AS BIOMARKERS OF AGING
Epigenetic clocks, specifically those measuring DNA methylation patterns, are utilized to quantify biological aging. These clocks analyze changes in methylation (the addition of methyl groups to DNA) across numerous sites in the genome. As people age, predictable patterns of methylation loss and gain occur, which can be used to estimate an individual's biological age. This measure offers a more precise reflection of aging than chronological age alone and can be applied across various tissue types, providing a consistent biomarker.
ADVANCEMENTS IN EPIGENETIC CLOCK TECHNOLOGY
Early epigenetic clocks, like the original Horvath clock, were trained to predict chronological age. However, second-generation clocks, such as Levine's PhenoAge and the GrimAge clock developed by others, are trained using biomarkers predictive of mortality or health span. This shift aims to create clocks that better capture the biological processes underlying disease and aging, offering greater predictive power for health outcomes and remaining life expectancy compared to simply predicting chronological age.
PREDICTIVE POWER AND MULTIDIMENSIONAL AGING
Epigenetic clocks, especially when measured in blood, demonstrate comparable predictive power for mortality and disease risk to traditional clinical biomarkers, but with the advantage of tissue-specific measurements. While current clocks are not yet adept at capturing individual organ-specific aging (e.g., metabolic vs. cardiac aging), research is progressing towards developing "systems clocks" that can proxy the aging of different organ systems, providing a more comprehensive and personalized understanding of an individual's aging profile.
EPIGENETIC AGE ACCELERATION AND ITS DRIVERS
Epigenetic age acceleration occurs when an individual's predicted biological age is significantly older than their chronological age, indicating a potentially faster aging process and increased health risks. While genetics plays a minor role (10-20%), environmental and lifestyle factors are primary drivers. These include socioeconomic status, smoking, exercise, diet (plant-based diets may decrease epigenetic age), sleep quality, and stress management. Factors like menopause also appear to accelerate epigenetic age.
CELLULAR REPROGRAMMING AND AGE REVERSAL POTENTIAL
The potential for reversing aging is being explored through cellular reprogramming techniques, inspired by Yamanaka factors. Full reprogramming can revert somatic cells to an embryonic-like pluripotent state, resetting epigenetic clocks to zero. Partial reprogramming aims to achieve age reversal without losing cell identity, showing promise in animal models for reversing some aging hallmarks and improving health span. While human applications are still speculative, this research highlights the dynamic nature of epigenetic aging.
PLASMA EXCHANGE AND THE CIRCULATING ENVIRONMENT
Research into plasma exchange and parabiosis experiments suggests that factors circulating in the blood play a role in aging. Exchanging plasma between young and old animals or growing cells in serum from different age groups indicates that the "old" environment can accelerate aging, while "younger" factors may offer a rejuvenating effect. This hints that accumulated substances in older blood might influence cellular aging, and their dilution or removal could partially reverse these effects.
LIFESTYLE INTERVENTIONS AND ACCURACY OF MEASUREMENT
Lifestyle changes, particularly exercise and a predominantly plant-based diet combined with intermittent fasting, are believed to influence epigenetic age. However, the accuracy and reliability of consumer-available epigenetic tests are debated. Early clocks exhibited high technical noise, leading to unreliable measurements. Newer methods and second-generation clocks aim to improve reliability and predictive validity, but consumers should exercise caution and consider traditional biomarkers alongside epigenetic tests for a comprehensive view of their health status.
THE FUTURE OF AGING RESEARCH AND PERSONALIZED HEALTH
The most exciting frontiers in aging research include understanding partial cellular reprogramming and the fundamental mechanisms driving epigenetic clock changes. The goal is to decipher what these clocks truly represent and how they functionally link to health outcomes. By developing more sophisticated and reliable tools, researchers aim to provide individuals with actionable insights derived from their biological age, guiding lifestyle decisions and paving the way for personalized interventions to promote longer, healthier lives.
Mentioned in This Episode
●Supplements
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●Companies
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●Books
●Studies Cited
●Concepts
●People Referenced
Common Questions
Chronological age is simply the number of years you've been alive. Biological age, however, refers to the physiological state of your body and how well its cells and systems are functioning, which can differ significantly from your chronological age.
Topics
Mentioned in this video
Biomarkers used to quantify the aging process by analyzing DNA methylation patterns.
A model organism (mouse) exhibiting premature and accelerated aging, used to study aging mechanisms and potential interventions.
Researcher who conducted a small study on an extreme dietary intervention showing epigenetic age reversal.
A hallmark of aging related to the protective caps on chromosomes becoming shorter over time.
Researcher whose group explored partial cellular reprogramming for age reversal.
A hallmark of aging related to how cells sense and respond to nutrients.
Researcher whose work on personalized aging profiles and different 'ager' types (metabolic, cardiac, immune) was discussed.
Adult cells that have been reprogrammed to an embryonic-like state, capable of differentiating into various cell types.
A company that developed and offers consumer epigenetic age tests, which Morgan Levine advised.
Changes in gene expression that occur without altering the underlying DNA sequence, considered a hallmark of aging.
A hallmark of aging where the body's supply of stem cells diminishes.
Four transcription factors (OSKM) that can reprogram adult somatic cells into induced pluripotent stem cells.
Aging based on the passage of time, as indicated by a birth date.
A long-term, ongoing cardiovascular health study used for research, including analysis of omega-3 index and life expectancy.
The changes a body undergoes over time, affecting risk of disease and function.
One of the hallmarks of aging, referring to damage to DNA.
A clinical biomarker measurement related to fat-like substances in the blood, often used in assessing health and disease risk.
Biotech company where Morgan Levine is a Principal Investigator, focused on understanding aging mechanisms and developing interventions.
Aging observed through physical capabilities and visible changes in the body.
A second-generation epigenetic aging clock tuned to mortality risk.
Aging measured by the ability to perform daily tasks and physical activities.
A second-generation epigenetic aging clock developed by Morgan Levine and colleagues, tuned to mortality and healthspan.
Connecting the circulatory systems of a young and an old animal to study the effects of blood exchange on aging.
A specific method of plasma exchange using saline and albumin, shown to rejuvenate old mice.
A dietary approach involving fasting for a specific period each day (e.g., 16 hours), often combined with calorie restriction.
A hallmark of aging where cells stop dividing and can contribute to tissue dysfunction.
Specific locations in the DNA where a cytosine is followed by a guanine, often methylated and relevant to epigenetic clocks.
A study, co-authored by Morgan Levine, showing that people age at different rates, with facial appearance correlating to biological age.
The phenomenon observed in studies where connecting circulatory systems of young and old organisms affects aging rates.
Researcher whose lab at UC Berkeley conducted studies on plasma dilution and rejuvenation.
A new book by Morgan Levine explaining biological age, its measurement, and lifestyle implications.
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