← The Peter Attia Drive
<p><a href="https://peterattiamd.com/denadubal/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240527-pod-denadubal&utm_content=240527-pod-denadubal-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240527-pod-denadubal&utm_content=240527-pod-denadubal-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240527-pod-denadubal&utm_content=240527-pod-denadubal-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer's disease.</p> <p><em>Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer's disease.</em></p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>Dena's fascination with aging and how she came to study klotho [3:30];</li> <li>Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45];</li> <li>Potential benefits of klotho on brain health [22:00];</li> <li>The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45];</li> <li>The role of platelet factor 4 (PF4) and it's interaction with GluN2B in mediating cognitive enhancement [46:45];</li> <li>Benefits of klotho observed in a mouse model of Parkinson's disease [55:45];</li> <li>Benefits of klotho observed in a mouse model of Alzheimer's disease [1:03:00];</li> <li>Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00];</li> <li>Speculating why a single klotho injection has such long-lasting effects [1:25:30];</li> <li>Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45];</li> <li>The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer's disease [1:34:45];</li> <li>The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15];</li> <li>Measuring klotho levels and determining an individual's KL-VS status [1:52:15];</li> <li>The promising potential of klotho for Alzheimer's disease treatment, and the importance of philanthropy for funding research [1:58:00]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Engage in Chronic Exercise
Regularly engage in chronic exercise, as it is a robust intervention shown to increase clotho levels by about 30% after 12 weeks, potentially enhancing brain health and longevity.
2. Manage Chronic Stress
Actively manage chronic stress, as high levels of stress are associated with lower clotho levels and shorter telomeres, suggesting a negative impact on aging markers.
3. Consider Rapamycin
Consider rapamycin as a potential intervention, as studies in mice show it can increase clotho levels, contributing to the convergence of biology for longevity factors.
4. Monitor Clotho Levels
Consider getting your clotho levels checked as a potential diagnostic biomarker, as lower levels are associated with increased mortality risk from diseases like cancer and cardiovascular disease.
5. Standardize Clotho Measurement
If getting clotho levels checked, ensure the blood draw is done in a morning fasting state to minimize diurnal variation and provide a more accurate and consistent measurement.
6. Pursue Big, Important Science
When conducting scientific research, aim for projects that are ‘big and important, and not incremental or mediocre,’ because both types of work will take the same amount of time.
7. Fund Risky, High-Upside Science
Philanthropists should fund scientific endeavors that are too risky for traditional funding but possess significant biologic plausibility and potential for transformative, game-changing impact.