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#10 - Matt Kaeberlein, Ph.D.: rapamycin and dogs — man's best friends? — living longer, healthier lives and turning back the clock on aging, and age-related diseases

Aug 20, 2018 1h 32m 14 insights
<p>Matt is someone who is deeply interested in understanding the biology of aging. Why do we age? What happens to us as we age? What are the things we can do to slow the aging process? How can we delay or prevent the onset of age-related diseases? These are all questions that Matt thinks deeply about, and explores these questions with his research at the University of Washington. He is currently investigating many of these questions through the Dog Aging Project and the compound rapamycin—the only known pharmacological agent to extend lifespan all the way from yeast to mammals—across a billion years of evolution. We talk about cancer, heart disease, Alzheimer's disease, healthspan, lifespan, and what we can do to provide longer, healthier lives for both people and dogs.</p> <p>We discuss:</p> <ul> <li>Matt's early years and his a-ha moment on aging [<a href="">4:00</a>];</li> <li>Studying dogs [<a href="">6:30</a>];</li> <li>Dogs, rapamycin, and its effects on lifespan and healthspan [<a href="">15:30</a>];</li> <li>An unexpected finding in presumably healthy dogs [36:00];</li> <li>Rapamycin in cancer treatment [50:00];</li> <li>Why isn't there a rapamycin trial for Alzheimer's disease (AD)? [1:01:30];</li> <li>If Matt could do a definitive study on life extension in dogs, with resources not being a concern, what does that experiment look like? [<a href="">1:16:00</a>]; and</li> <li>More.</li> </ul> <p> <span> Learn more at <a href="http://www.peterattiamd.com/"><span><u>www.PeterAttiaMD.com</u></span></a></span></p> <p> <span>Connect with Peter on <a href=""> <span> <u>Facebook</u></span></a> | <a href=""> <span> <u>Twitter</u></span></a> | <a href=""> <span> <u>Instagram</u></span></a>.</span></p>
Actionable Insights

1. Rapamycin for Immune Rejuvenation

Consider short-term rapamycin treatment (e.g., 6-10 weeks) followed by a 2-week washout period to potentially restore immune function, as evidenced by improved vaccine response in aged mice and people.

2. Rapamycin for Cardiac Rejuvenation

Rapamycin treatment for 6 to 10 weeks has been shown to improve heart function in aged mice, restoring it halfway to youthful levels, with benefits observed while the treatment is ongoing.

3. Rapamycin for Early Cognitive Decline

For individuals experiencing mild cognitive impairment, rapamycin may offer a promising intervention to improve cognitive function and potentially reduce amyloid accumulation, based on studies in aged animals and Alzheimer’s disease mouse models.

4. Rapamycin Rejuvenates Multiple Tissues

Rapamycin has demonstrated a rejuvenating effect, not just delaying decline, but improving function back towards a more youthful state in areas like immune function, cardiac function, intestinal stem cells, and alveolar bone levels, likely through stem cell mediation.

5. Rapamycin Dosing for Healthy Dogs

For healthy, middle-aged dogs (at least 40 pounds and 6 years old), a rapamycin dosing strategy of 0.1 mg/kg or 0.05 mg/kg given three times a week (e.g., Monday, Wednesday, Friday) showed no significant side effects over 10 weeks and improved heart function.

6. Monitor Long-Term Rapamycin Use

If considering long-term rapamycin treatment, especially for conditions like declining cardiac function, continuous monitoring (e.g., echocardiograms every three months) is recommended to assess efficacy and detect any potential side effects.

7. Rapamycin Enhances Cancer Surveillance

Boosting age-related immune function with rapamycin can enhance immune surveillance, which is a potent anti-cancer mechanism, suggesting a role for rapamycin in cancer prevention.

8. Avoid High-Dose Rapamycin

Extremely high doses of rapamycin may have detrimental effects on the immune system, potentially promoting certain aggressive cancers, as observed in female mice, highlighting the importance of dose optimization.

9. Improve Intestinal Barrier Function

Improving age-related decline in intestinal barrier function can reduce systemic inflammation, which is a significant contributor to aging, and rapamycin may play a role in this improvement.

10. Rapamycin Benefits are Dose-Dependent

Both the beneficial effects and potential side effects of rapamycin are strongly linked to its dose, with trough levels potentially correlating most strongly with side effects, emphasizing the need for careful dose titration.

11. Explore Metabolome for Biomarkers

To identify predictive signatures for anti-aging interventions like rapamycin, focus research efforts on the serum metabolome, as it is a promising area for correlating with functional effects and lifespan.

12. Conduct Short-Term Human Trials

To build evidence for rapamycin’s effects in humans, conduct short clinical trials (e.g., 6-10 weeks) in healthy elderly individuals, focusing on impactful functional outcomes like immune function, cardiac function, or alveolar bone levels.

13. Listen to Sabatini Podcast

For listeners seeking foundational knowledge on mTOR and rapamycin, it is recommended to listen to the podcast with David Sabatini, as it provides essential background information.

14. Visit Peter Attia MD Website

To access additional details on podcast episodes and related topics, visit Peter Attia MD’s official website, peteratiyahmd.com.