In Addition to Healthy Lifestyles, Certain Medications Slow Aging
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 Ph.D. 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.
What works and what doesn’t
Improved blood-based DNA tests indicate that these 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.
- Healthy diet and exercise combined. Researchers looked at popular diets including, the Mediterranean, low-fat, and low-carb plans.
Additional research is needed to further validate the findings.
Today, Raghav’s research focuses on the biological systems that drive human aging and how to best measure aging, as well as why aging gives rise to diseases like cancer, diabetes, and dementia. And while his research might not necessarily solve aging, he does explore whether the aging process can be reversed through interventions.
Sehgal is the first author of a new paper from the lab of Albert Higgins-Chen, assistant professor of psychiatry in the Yale School of Medicine. In the paper, Higgins-Chen’s research team took a significant step toward determining which existing anti-aging 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 don’t have much effect. All members of the Higgins-Chen lab collaborated in the work, including researchers Daniel Borrus, Jenel F. Armstrong, John Gonzalez, Jessica Kasamoto, and Yaroslav Markov. The paper appears in the journal Nature Medicine.
“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. As people age, these chemical tags change, previous research has shown. Successful anti-aging interventions can reverse the tags. Computer algorithms are then able to use the changes observed in these tags to estimate a person’s epigenetic “age.”
In their work, the researchers combined data from 51 anti-aging 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 health span and lifespan. There is data from retrospective analysis 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 intervention: 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 it’s 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 tumour necrosis factor, is an immune-system protein that helps fight inflammation-related injury.)
On the other hand, over-the-counter supplements and certain medical procedures didn’t 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 would be expanded testing measuring interventions and 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 anti-aging 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.”
Senior author Higgins-Chen warned that researchers need to be cautious in interpreting intervention studies.
“We have developed a rigorous, systematic approach to evaluating and comparing how biomarkers change across a wide variety of interventions, and that is a critical step in the right direction,” he said. “However, the true meaning of that change must be fully understood.”
Which biomarker changes are due to the intervention, and which result from hidden confounders? What is the time course of the change during an intervention – and after the intervention ends? What are the biological mechanisms underlying the change?
“And most importantly – what does the change mean for our long-term risk of age-related disease and functional decline?” Higgins-Chen said. The lab is continuing to investigate these questions in additional studies led by researchers Borrus, Armstrong and Grace Zou. Chen’s lab is also affiliated with the Department of Pathology, the Computational Biology and Bioinformatics Program, and the Y-Age Yale Center for Research on Aging.
Source: Yale University
