Podcast Summary: "Reverse Aging Now: The Latest Longevity Breakthroughs | Dr. Eric Verdin"

Episode Release Date: December 4, 2024

Introduction

In this enlightening episode of The Dr. Hyman Show, host Dr. Mark Hyman engages in a deep and comprehensive conversation with Dr. Eric Verdin, President and CEO of the Buck Institute for Research on Aging. Together, they explore the cutting-edge advancements in longevity research, delving into the biological mechanisms of aging, innovative therapies, and practical interventions to extend both lifespan and healthspan.

The Evolution of Aging Research

Dr. Hyman opens the discussion by highlighting the historical neglect of aging as a field of medical research. Traditionally viewed as an inevitable decline, aging was often dismissed as too complex or "messy" to study, leading to its categorization as the "backwaters of biology" about 25 to 30 years ago.

Dr. Verdin emphasizes the paradigm shift that has occurred over the past few decades:

"About 25, 30 years ago, aging was considered sort of the backwaters of biology. This was an area that you did not go there because it was considered too messy." ([07:01])

He explains that breakthroughs in identifying mutations that extend lifespan in model organisms like C. elegans, fruit flies, and mice challenged the prevailing notions, revealing that longevity could indeed be scientifically manipulated. This foundational research paved the way for modern gero-science and longevity studies, which now show promise in translating these findings to humans.

Measuring Biological Age

Dr. Hyman brings up the concept of biological age versus chronological age, underscoring the importance of accurate biomarkers in assessing aging and the effectiveness of interventions:

"I went back, even though I got two years older. Now I'm 64 on the same test I went to from 43 when I was 62 to 39 when I'm 64." ([16:51])

Dr. Verdin discusses the emergence of various biological clocks, particularly epigenetic clocks that measure DNA methylation. He notes the variability among different clocks and the necessity of consistent measurement methods:

"There's been a lot of interest in the field of generating more precise and more predictive biomarkers of biological age..." ([19:56])

He advocates for repetitive measurements over time to track changes accurately, despite the current inconsistencies among different clock types.

Longevity Pathways and Mechanisms

Shifting focus to the underlying mechanisms of aging, Dr. Hyman introduces the concept of "longevity switches"—key nutrient-sensing pathways such as mTOR, insulin signaling, AMPK, and sirtuins. These pathways play a pivotal role in regulating various hallmarks of aging, including mitochondrial function, inflammation, and DNA repair.

Dr. Verdin concurs, highlighting the interconnectedness of these pathways:

"There's one theory of aging that posits that one of the things that happens as we age is our ability to generate energy decreases." ([34:17])

He stresses the complexity of biological systems and the challenge of identifying the highest leverage points for intervention, emphasizing that lifestyle factors like nutrition and exercise have profound impacts on these longevity pathways.

Mitochondrial Function and Aging

A central theme of the discussion is the role of mitochondria in aging. Dr. Hyman illustrates their importance by comparing the vitality of young and elderly individuals to the health of their mitochondrial function:

"The difference between a two-year-old who's running around like crazy... versus a 92-year-old who's just sitting in the chair, barely can move, is the health and function of their mitochondria." ([34:17])

Dr. Verdin explains that mitochondrial numbers and functionality decline with age, leading to an energy deficit that affects cellular repair processes. He advocates for interventions such as intermittent fasting and mitochondrial biogenesis supplements to enhance mitochondrial function:

"Intermittent fasting... activates a process called autophagy... to keep the ones that are most efficient." ([38:31])

NAD and Its Role in Aging

The conversation delves into the significance of Nicotinamide Adenine Dinucleotide (NAD) in cellular energy metabolism. Dr. Verdin elucidates the challenges and misconceptions surrounding NAD supplementation:

"NAD is an intracellular molecule. It doesn't cross from the blood into your cells... intravenous NAD does not make much biological sense." ([44:31])

He points out that while NAD levels decline with age, simply supplementing with precursors like NMN or NR in inadequate doses may offer limited benefits. Instead, he advocates for the development of CD38 inhibitors to prevent NAD degradation:

"You're essentially filling up more water in the leaky sink... better to just put the hole in the bucket." ([51:25])

Dr. Verdin also cautions against unregulated supplementation without medical supervision, highlighting potential adverse effects such as increased homocysteine levels.

Supplements and Cautions

Dr. Hyman and Dr. Verdin discuss various supplements purported to influence longevity, evaluating their efficacy and safety. Dr. Verdin stresses the importance of foundational health practices—adequate nutrition, exercise, sleep, and stress management—before considering supplementation:

"We do not have and will not have for the next 20 years an anti-aging medicine or supplement that is better than physical activity." ([58:01])

He highlights omega fatty acids and urolithin A as some of the more promising supplements, while advising caution against the overuse of multiple supplements ("polypharmacy") due to unpredictable interactions and side effects.

Future of Aging Research

Looking ahead, Dr. Verdin expresses excitement about the integration of systems biology and artificial intelligence in aging research. He envisions a future where phenomics—comprehensive profiling of phenotypes—allows for personalized and preventative medicine:

"We are ramping up to the next stage data gathering and processing." ([65:37])

This advancement will facilitate deeper understanding and more targeted interventions, potentially revolutionizing how aging and related diseases are managed.

Conclusion

The episode concludes with Dr. Hyman and Dr. Verdin emphasizing the dual approach of optimizing current health through proven lifestyle interventions while eagerly anticipating future scientific breakthroughs that could further extend healthy lifespans. Dr. Hyman reflects on the significance of ongoing research and its potential to transform health paradigms:

"We're in the most exciting era... I just can't wait to see what's going to happen." ([67:58])

Dr. Verdin concurs, urging listeners to prioritize current health practices to benefit both present and future well-being:

"Keep yourself healthy and you will reap the benefits now and in the future." ([68:45])

Key Takeaways

• Aging as a Scientific Field: Aging research has evolved from a neglected discipline to a burgeoning field with significant breakthroughs in understanding longevity mechanisms.

• Biological vs. Chronological Age: Accurate biomarkers are essential for assessing biological age and the effectiveness of anti-aging interventions.

• Longevity Pathways: Key nutrient-sensing pathways (mTOR, insulin signaling, AMPK, sirtuins) serve as central regulators of aging and are potential targets for interventions.

• Mitochondrial Health: Maintaining mitochondrial function is crucial for energy generation and cellular repair, making it a primary target for anti-aging strategies.

• NAD Metabolism: While NAD levels decline with age, effective strategies to preserve or restore NAD require advanced approaches beyond simple supplementation.

• Supplementation Caution: Prioritize foundational health practices before considering supplements, and be wary of polypharmacy and unregulated supplement use.

• Future Prospects: Integration of systems biology and AI promises to revolutionize aging research, enabling more personalized and preventative healthcare.

This episode provides a comprehensive overview of the current state and future directions of aging research, offering valuable insights for listeners interested in longevity and healthspan enhancement.