Groundbreaking Yale and TruDiagnostic Study Compares 51 Interventions to Slow Aging Across Multiple Biological Clocks

LEXINGTON, Ky., Oct. 28, 2024 /PRNewswire/ -- In a landmark collaboration between Yale University and epigenetics company TruDiagnostic, a new study has analyzed the impact of over 51 interventional trials with DNAm biological aging clocks, making it the first large scale meta-analysis of aging interventions. This unprecedented research systematically analyzed the impact of 51 different longevity interventions–spanning diet, exercise, pharmacological, and therapeutic modifications–on 110 biomarkers including biological age clocks and epigenetic biomarker proxies to identify which are most effective at slowing aging. This is the first time a study has compared multiple therapeutic interventions in a single analysis across multiple biological age testing methods.

Age is the number one risk factor for most chronic diseases and death across the world. Epigenetics–the way our genes express themselves based on our environment–has emerged as a leading method to evaluate how our body is aging at the cellular level using advanced algorithms known as 'biological age clocks'. While these clocks previously have been able to tell us whether we're aging faster or slower than we should, this research unlocks concrete actions for improvement.

"We are extremely excited to release this research because it adds a level of transparency to discussions on biological age. Previously, biological age testing companies could only tell you your estimated biological age using epigenetic clocks. Now we can suggest ways to slow down these epigenetic clocks with interventions using real world data," Ryan Smith, Co-Founder of TruDiagnostic and Head of its Research & Development.

Senior author Albert Higgins-Chen, MD, PhD, Assistant Professor at Yale University, states this work can guide the aging field moving forward: "It is still unclear whether these short-term epigenetic clock changes over months will translate into long-term health benefits over decades, which is what we ultimately care about. However, studies to determine the long-term benefits will be lengthy and expensive. Our work will guide the next generation of geroscience clinical trials by helping researchers identify the highest-priority interventions based on current knowledge and select the best subset of clocks to test those interventions."

Yale PhD candidate and co-corresponding author of the study, Raghav Sehgal, emphasizes the critical nature of their research for two key reasons: "First, this study establishes a new standard by directly comparing longevity interventions in humans. By evaluating 51 interventions across numerous biomarkers, it enables us to answer complex questions that single-intervention studies cannot—such as determining which biomarkers are responsive to specific types of interventions and which align on the effects of these interventions. Second and most importantly, it highlights that the responsiveness of DNAm aging biomarkers cannot be assumed without systematic testing." He adds, "We hope this work encourages the field to rigorously test DNAm aging biomarkers for responsiveness and sets new standards moving forward."

So which interventions actually work? Among the 51 interventions that high priority for further validation to reduce aging according to the epigenetic clock, below are a few key findings:

1. Pharmacological Interventions Drive Greatest Impact:

• • The study found that pharmacological treatments—such as anti-TNF therapies and metformin—consistently showed the strongest impact on reducing epigenetic age across multiple clocks in HIV patients.
  • Anti-TNF therapies, used to treat autoimmune diseases, significantly reduced biological age markers across several studies, indicating that inflammation plays a critical role in the aging process. This supports the growing understanding that reducing chronic inflammation could be a major pathway to slowing aging.

2. Lifestyle Interventions Show Strong Results:

• • Lifestyle changes, such as dietary adjustments and exercise, also showed promising results, especially Mediterranean diets, which consistently reduced biological age markers across multiple systems.
  • These findings suggest that dietary choices—rich in antioxidants and healthy fats—can have a profound impact on slowing aging, particularly in key systems like cardiovascular and metabolic health.
  • Out of all clocks, DunedinPACE was the most responsive to Lifestyle interventions.

3. Senolytic Drugs Show Inconsistent Results:

• • While certain senolytic drugs (designed to eliminate aging cells) showed promise in early studies, the results were inconsistent across multiple trials. Some studies reported increases in biological age, suggesting that more research is needed before these therapies can be widely recommended for anti-aging purposes.
  • This is a significant finding for the longevity community, as it calls for a cautious approach to senolytics and highlights the need for more targeted therapies.

4. Targeted System Health:

• • Specific biological systems benefit more than others from interventions, and TruDiagnostic's SymphonyAge Systems and OMICmAge clocks offer the ability to track these changes with precision. For example, smoking cessation showed the greatest improvements in lung health, while metformin had a broad impact on metabolic and inflammatory markers, proving it to be a powerful multi-system intervention for aging. These advanced clocks allow us to pinpoint how interventions impact different systems, such as cardiovascular, immune, and neurocognitive health.
  • By utilizing these specialized clocks, users can track not just their overall biological age but also which specific body systems may need more attention, providing a deeper and more personalized path to healthier aging.

Why These Findings Matter: This research is the first meta-analysis of its kind. Biological aging cocks have been created to give us a measuring stick for real-time health data, so we don't have to wait 40+ years to see how interventions help people. This is the first major head-to-head comparison of these clocks.

The results from the comparison are clear: TruDiagnostic's commercial "GenX clocks" such as OMICmAge (Developed with Harvard) and SymphonyAge (Developed with Yale) are the most responsive and effective available. "GenX clocks", which refer to a new class of explainable biological age clocks that offer more detailed, system-specific insights into how different parts of the body are aging. These clocks provide subscores for different biological systems, allowing users to track specific areas like metabolic, immune, or cardiovascular health. This means that for the first time, consumers, clinicians, and researchers can rely on validated interventional data to make decisions that enhance their longevity and overall well-being.

About TruDiagnostic

TruDiagnostic is a leading health data company and CLIA-certified laboratory specializing in epigenetic testing and research. Home to the largest private DNA methylation database globally, TruDiagnostic partners with notable biotech developers, researchers, and academic institutions to transform the healthcare potential of epigenetic data into actionable applications. The company's TruAge biological aging tests offer the most in-depth results, helping individuals and healthcare providers make informed lifestyle and medical decisions based on insights found in the fluid epigenome.

For more information about TruDiagnostic, please visit www.trudiagnostic.com.

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Frequently Asked Questions:

1. What is the significance of this study?

This study is groundbreaking because it is the first time multiple lifestyle and therapeutic interventions have been analyzed across several biological aging clocks simultaneously. The findings validate specific interventions for slowing down biological aging, offering concrete, data-driven insights into what works for improving longevity. Additionally, the study demonstrates that TruDiagnostic's aging clocks—DunedinPACE and Symphony Age—are the most responsive aging clocks available, and these changes are trustworthy because their changes are usually backed up by multiple other clocks.

2. What are "GenX" clocks?

"GenX clocks" refer to a new class of explainable biological age clocks that offer more detailed, system-specific insights into how different parts of the body are aging. These clocks provide subscores for different biological systems, allowing users to track specific areas like metabolic, immune, or cardiovascular health. TruDiagnostic's OMICm Age and Symphony Age clocks fall into this "GenX" category and are designed to give more actionable, explainable data compared to traditional single-score aging clocks.

3. What interventions were studied, and what were the key findings?

The study examined 51 different interventions, ranging from lifestyle changes (like diet and exercise) to pharmacological treatments (like anti-TNF therapies and metformin). Some key findings include:

• Pharmacological interventions, particularly anti-TNF therapies (which reduce inflammation) and metformin (a drug that improves metabolic function), had the most consistent and significant impact on reducing biological age.
• Lifestyle changes, especially Mediterranean diets, showed strong results, particularly in improving metabolic and cardiovascular health.
• Senolytic drugs, which are designed to eliminate aging cells, showed inconsistent results, with some interventions increasing biological age in certain studies.

4. How do TruDiagnostic's clocks perform compared to other aging clocks?

TruDiagnostic's clocks—OMICm Age and Symphony Age—outperformed all other aging clocks in the study. They were the most sensitive to changes from interventions and provided more explainable insights, thanks to their subscores for different biological systems. This makes them more effective for tracking both the overall rate of aging and the health of specific body systems, such as immune or metabolic health.

5. What makes this study different from other aging research?

This study is unique because it is the first time so many diverse interventions have been systematically tested across multiple biological clocks. Previous studies focused on individual interventions or a small number of clocks, making it difficult to compare results. This comprehensive approach not only validates specific interventions but also reveals which aging clocks are the most accurate and responsive, providing a much-needed standardized framework for future aging research.

6. Why are the results of this study important for consumers?

The findings give consumers clear, actionable insights into which interventions can help them slow aging and improve their healthspan (the years they live in good health). Many of the interventions validated in the study, such as dietary changes and pharmacological treatments, are accessible to the public and can be integrated into their daily lives. Additionally, TruDiagnostic's TruAge biological age test measures the same biomarkers examined in the study, offering consumers a way to track their progress and see how these interventions affect their biological age.

7. What specific interventions were shown to slow aging?

The study validated several interventions that significantly reduce biological age, including:

• Anti-TNF therapies: These treatments, typically used for autoimmune conditions, consistently reduced biological age markers by reducing inflammation.
• Metformin: Widely used for diabetes, metformin was shown to improve metabolic and inflammatory markers and reduce biological age.
• Mediterranean diets: These diets, rich in healthy fats and antioxidants, improved biological aging markers, especially in metabolic and cardiovascular systems.

8. What are the limitations of the study?

While the study is comprehensive, it primarily focuses on DNA methylation-based aging clocks, which are just one type of aging biomarker. Additionally, aging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention, without the need for decade-spanning trials, by acting as surrogate endpoints, but the results need to be validated in longer-term studies to fully understand how these clocks predict long-term health outcomes. Additionally, some interventions, such as senolytic drugs, showed inconsistent results, suggesting that further research is needed to fully understand their impact on aging.

9. What are "explainable" aging clocks, and why are they important?

"Explainable" aging clocks, like the GenX clocks featured in this study, provide subscores for different systems in the body, such as immune, metabolic, and cardiovascular health. This allows users to see which parts of their body are aging faster and target specific interventions to slow aging in those areas. This is a major advancement over traditional single-score clocks, which only give an overall biological age without explaining which systems are most impacted.

10. How do these findings impact the future of aging research?

This study sets a new standard for aging research by showing that DNA methylation clocks can be used to validate aging interventions. It provides a roadmap for future clinical trials, identifying which biomarkers and interventions should be prioritized for testing. The study also proves that certain interventions—like anti-TNF therapies and Mediterranean diets—have consistent effects on slowing biological aging, opening the door to more targeted, science-backed treatments for longevity.

11. How do TruDiagnostic's products benefit from this research?

TruDiagnostic's products, including TruAge biological age test, use the same biomarkers tested in this study. This means that customers using these tests will have access to validated, actionable data that can help them improve their health and longevity. The research directly supports the effectiveness of the biomarkers TruDiagnostic tests for, ensuring that consumers are receiving science-backed insights into their biological aging process. Aging is complex and TruDiagnostic continues to generate and publish data so people can take a science based approach to improve the aging process.

12. How was this study conceived with Yale collaborators?

The Higgins-Chen lab was already investigating when to trust epigenetic clock changes using publicly available data, suspecting there are particular interventions and clocks that are more trustworthy than others. However, while working with TruDiagnostic to implement SYMPHONYAge, we realized there was revealed an opportunity to expand this analysis to far more interventions and clocks using datasets that TruDiagnostic had generated with a variety of collaborators.

13. What's next for TruDiagnostic and Yale's collaboration?

Following this groundbreaking study, TruDiagnostic and Yale plan to continue their research into biological aging, with the goal of developing even more refined and actionable aging interventions. The collaboration will likely focus on expanding the range of biomarkers tested (including the development of novel biomarkers optimized for responsiveness) and further validating interventions that can slow aging, with a focus on translating these findings into practical, real-world applications for consumers.

14. What is Epigenetics?

Genetics is the study of our DNA, and epi- is a Greek prefix for "above." Together, epigenetics describes molecular interactions immediately above the genome, and encompasses how the instructions of life coded in our DNA are actually put to use throughout our body.

This regulation of our genes allows your body to pick and choose what instructions get used, what gets tweaked, and what gets skipped all together.

Compared to genetics, epigenetic information is often more useful when it comes to understanding and treating health related matters. This is because epigenetics allows us to see the behavior of genetic material, not just what it contains. You can think of our genetics like a lamp or light source, with our epigenetics being the switch that turns said light on, off, or somewhere in between (like a dimmer).

15. What is DNA methylation?

There are several ways that DNA regulation (epigenetics) can occur in the cells throughout your body, with one of the most prominent methods being DNA methylation. DNA methylation is a process where molecules (methyl molecules) attach to sections of your DNA. This process can be thought of as the "turning off" or dimming of the instructions at that gene location.

Broadly speaking, methylation is not considered good or bad as it pertains to your health and wellness because every gene has a specific function and might need to be turned off or turned on according to individual circumstances. For instance, "turning off" oncogenes genes (genes linked to cancer) through more DNA methylation might be considered good for your health, while "turning off" tumor suppressor genes (genes which suppress cancer) might be considered bad.

Of the 28 million+ CpG locations of the human genome, up to 80% are methylated to some degree. As we age, the extent of DNA methylation at these various spots change and form patterns. Researchers have been successfully able to link millions of these patterns to specific ages, and age-related health outcomes. For example, if 2,000 patients show methylation on their DNA at the same place, and 1,999 of those patients develop Alzheimer's, we can say with a high degree of certainty that evaluating methylation patterns on that particular section of DNA can help predict someone's risk of developing Alzheimer's.

SOURCE TruDiagnostic