.jpg)
A new Yale analysis found that diet, exercise, and some medications can slow the aging process, while over-the-counter supplements appear to have little effect.
Photo Credit: Alena Darmel
Scientific Frontline: Extended "At a Glance" Summary: Epigenetic Anti-Aging Interventions
The Core Concept: A comprehensive analysis of anti-aging intervention studies utilizing blood-based DNA tests, known as epigenetic clocks, to determine which therapies genuinely slow the biological aging process.
Key Distinction/Mechanism: Unlike chronological age, epigenetic clocks estimate biological age by analyzing the patterns of methyl groups (chemical tags) attached to a person's DNA. Effective interventions can reverse these chemical markers, providing a measurable indicator of biological age reduction.
Major Frameworks/Components:
- Pharmacological Interventions: Prescription medications used for metabolic control and weight management, including metformin, semaglutide, and anti-TNF therapies, were highly effective at decreasing epigenetic age.
- Lifestyle Changes: The combination of exercise and a healthy diet, such as Mediterranean, low-fat, and low-carbohydrate plans, consistently decreased epigenetic age.
- Over-the-Counter Supplements: The analysis demonstrated that non-prescription supplements and certain medical procedures had little to no measurable effect on biological aging.
- Biomarker Evolution: The research evaluated over 110 DNA methyl biomarkers and concluded that newer biological age clocks significantly outperformed older models.
Branch of Science: Epigenetics, Computational Biology, Bioinformatics, and Gerontology.
Future Application: Validating these epigenetic biomarkers will allow scientists to evaluate the long-term effectiveness of new anti-aging therapies in just a few months or years, circumventing the need for decades-long clinical trials.
Why It Matters: By establishing quantifiable evidence that specific lifestyle changes and medications can reverse biological age, researchers can prioritize proven therapies to combat age-related diseases, such as cancer, diabetes, and dementia.
.jpg) |
| From left to right: Daniel Borrus, Grace Zhou, Raghav Sehgal, Jenel Armstrong, Albert Higgins-Chen, and Avery Hanson, members of the Higgins-Chen lab research team at the Yale School of Medicine, standing in front of posters presenting their work on epigenetic biomarkers of aging and the TranslAGE framework that they have shared at multiple scientific conferences. Photo Credit: Allie Barton |
When Raghav Sehgal arrived at Yale as a graduate student several years ago, he wanted to explore the use of powerful computer science tools in cancer research. With an engineering background and a computational biology startup already under his belt, he was well prepared.
But as Sehgal began his PhD studies, his thesis adviser at the Yale School of Medicine posed a larger question: If you want to solve cancer or any age-related disease, such as cardiovascular disease, why not solve aging itself?
“That put me on a different path,” said Sehgal, an associate research scientist in psychiatry with specialties in computational biology and bioinformatics. “As researchers, we have a long way to go in understanding the aging process and whether the steps we take to manage it really work.”
- Improved blood-based DNA tests indicate that the following interventions seem to be the most effective at slowing the biological aging process:
- Prescribed medications for metabolic control and weight management, including metformin and semaglutide.
- A combination of a healthy diet and exercise. Researchers examined popular diets, including the Mediterranean, low-fat, and low-carb plans.
Additional research is needed to validate these findings further.
Today, Sehgal’s research focuses on the biological systems that drive human aging and how best to measure aging, as well as why aging gives rise to diseases like cancer, diabetes, and dementia. While his research might not necessarily solve aging, he explores whether the aging process can be reversed through interventions.
In a new paper published in the journal Nature Medicine, Sehgal’s research team took a significant step toward determining which existing antiaging measures have quantifiable impacts. Using a new class of DNA-based blood tests, they found that lifestyle interventions and certain drug treatments indeed appear to slow the aging process, while over-the-counter supplements do not have much effect.
.jpg) |
| A DNA methylation microarray, which measures DNA methylation at hundreds of thousands of sites across the genome. Researchers use data generated from these arrays to develop and evaluate epigenetic clocks and other biomarkers of biological aging. Photo Credit: Allie Barton |
“For the first time, we’ve shown that certain therapies have measurable impacts,” said Sehgal. “This wasn’t previously possible because we didn’t have enough data to say these biomarkers are consistently responsive to these interventions.” Biomarkers are measurable indicators that reflect a person’s functional or biological age rather than just the number of years lived.
For their analysis, the researchers primarily used a type of blood-based biomarker known as epigenetic clocks, which estimate epigenetic or biological age by measuring the pattern of methyl groups (basic chemical structures that act like tags) attached to a person’s DNA. Previous research has shown that as people age, these chemical tags change. Successful antiaging interventions can reverse the tags. Computer algorithms can then use the changes observed in these tags to estimate a person’s epigenetic “age.”
In their work, the researchers combined data from 51 antiaging intervention studies—which examined a range of strategies, from supplements to medical procedures—and measured more than 110 DNA methyl biomarkers (including 16 major epigenetic clocks). They then compared participants’ biological ages before and after various interventions.
“What we did was pretty unique,” Sehgal said. “We already know that certain things might prolong healthspan and lifespan. There are data from retrospective analyses as well as from animal models. We took all that knowledge along with the real-world clinical studies to identify which interventions in humans were slowing down aging across the board in these known biomarkers.”
The researchers tested four categories of interventions: pharmacological drugs, lifestyle-based changes, over-the-counter supplements, and medical procedures. They found that lifestyle interventions, such as a combination of a healthy diet (whether Mediterranean, low-carb, or low-fat) and exercise, consistently decreased epigenetic age.
Pharmacologic interventions—including metformin and semaglutide, prescription medications used for metabolic control and weight management, and anti-TNF therapies, which use biologic medications to target an immune system protein that triggers harmful inflammation—decreased epigenetic age the most. (TNF, or tumor necrosis factor, is an immune system protein that helps fight inflammation-related injury.)
Conversely, over-the-counter supplements and certain medical procedures did not have an effect in decreasing epigenetic age, their analysis showed. Other key findings revealed that the newer biological age clocks outperformed older models and that biomarkers changed more in people with diseases than in healthy volunteers.
Going forward, the next step will be expanded testing to measure interventions and their impact in a widespread, diverse group of volunteers, Sehgal said.
“If these new biomarkers are eventually validated to predict long-term health, scientists will be able to evaluate antiaging therapies much faster,” he added. “Instead of waiting decades for evidence from clinical trials, we’ll be able to see which interventions are effective and in which people in a few years or even months.”
Published in journal: Nature Medicine
Title: Responsiveness of epigenetic aging biomarkers to longevity interventions in humans
Authors: Raghav Sehgal (राघव सहगल), Daniel Borrus, Jenel F. Armstrong, John Gonzalez, Jessica Kasamoto, Yaroslav Markov, Ahana Priyanka, Ryan Smith, Natàlia Carreras-Gallo, Jessica Lasky-Su, Varun B. Dwaraka, Michael J. Corley, and Albert Higgins-Chen
Source/Credit: Yale University | Karen Guzman
Edited by: Scientific Frontline
Reference Number: epig082226_01