Democratizing Longevity • GLP-1 Microdosing • SGLT2 Insights • Debate on Aging's Foundations

Your sneak peek into the world of Longevity Docs.

Hey Docs,

Writing to you from Novato, just a few minutes away from the Buck Institute for Research on Aging, where the Longevity Clinics Roundtable Conference took place. This week, I had the privilege of meeting some of the most incredible minds in longevity medicine: physicians, scientists, and entrepreneurs from leading clinics such as Longevity Center, Fountain Life, Human Longevity, Private Medical, and Chi Longevity. Together, we discussed the future of longevity medicine and the challenges ahead.

Here are my three key takeaways to democratize longevity medicine:

Three Key Takeaways to Democratize Longevity Medicine

1. Education as the foudantion
   Democratizing longevity medicine starts with education. Every physician should be equipped with cutting-edge knowledge of diagnostics, interventions, and treatments. Geroscience and the principles of longevity care should become a foundational part of medical school curriculums and be integrated across all specialties. Every doctor must also become a medical conductor—capable of orchestrating comprehensive, evidence-based longevity strategies for their patients.

2. Research as the evidence
   Dr. Dobri Kiprov emphasized, “Without clinical trials, this is just mythology.” Advancing the field requires large-scale, real-world evidence and rigorous clinical trials to validate therapies and protocols. Research is the cornerstone of progress—it enables validation, scalability, and accessibility by driving insurance coverage and reducing costs, ultimately making longevity medicine more widely available.

3. Standardization for the future
   As the field of longevity medicine evolves (and we are still in its early days), developing standardized protocols and practices is essential. These will provide the foundation for establishing longevity medicine as a recognized specialty, ensuring consistency, credibility, and long-term growth.

A balanced approach: efficacy, safety, and innovation
Above all, we must privilege efficacy and safety without stifling innovation. By balancing these priorities, we ensure meaningful, responsible advancements that drive the field forward while maintaining trust and delivering real impact.

PS; And just a little reminder from the conference: exercise and sleep remain the most validated longevity interventions—outperforming many therapies and supplements. Let’s not forget the basics! 😉

Happy Sunday!
Dr. David Luu

… was so cool to meet so many Longevity Docs

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This Week’s Highlights

👋 Community News

• Weekly Pulse

🎓 Masterclass

5 Key Takeaways from the Masterclass on SGLT2 Inhibitors

1. Mechanisms of SGLT2 Inhibitors:

   • SGLT2 inhibitors reduce glucose reabsorption in the kidneys, promoting glucose excretion and improving glycemic control.

   • They enhance energy efficiency by improving fatty acid oxidation, mitochondrial health, and reducing inflammation and oxidative stress.

   • The inhibitors work synergistically with AMPK activation and mTOR inhibition, key pathways in longevity medicine.

2. Cardiovascular and Renal Benefits:

   • SGLT2 inhibitors improve heart failure outcomes by reducing preload and afterload, enhancing myocardial function, and promoting natriuresis without significant intravascular volume depletion.

   • They protect kidney function by reducing glomerular hyperfiltration and renal fibrosis, with potential applications in preventing nephrolithiasis.

3. Potential in Longevity and Metabolic Health:

   • These inhibitors mimic calorie restriction effects, offering benefits like improved autophagy, senolysis, and reduced insulin and IGF-1 signaling.

   • They have promising roles in improving gut microbiota, reducing visceral fat, and positively influencing biomarkers like uric acid and inflammatory mediators.

4. Application in Non-Diabetic Populations:

   • SGLT2 inhibitors can be effectively stacked with other longevity agents like metformin and GLP-1 agonists for non-diabetic patients focused on longevity and metabolic optimization.

   • They show potential for reducing amyloid plaques, tau proteins in dementia, and inflammation in post-stroke recovery.

5. Safety Profile and Side Effects:

   • While generally well-tolerated, risks include genital mycotic infections and rare occurrences of euglycemic ketoacidosis, particularly in diabetic or calorie-restricted individuals.

   • Patient-specific factors guide the choice of specific inhibitors, e.g., empagliflozin for cardiac patients and canagliflozin for broader longevity benefits. Proper monitoring and context-specific use are crucial for safety.

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💬 Buzz in the Chat

How are you all thinking about microdosing glp1 for metabolic health, CV and neurodegen disease prevention?

• Depends on the individual but I think tirzepatide 2.5mg q weekly for a 3 month cycle can do wonders

  Important to measure biomarkers pre and post

  The key with micro dosing glps in my experience is mitigating the initial side effects and getting them to complete 3 months of therapy

  In the micro dosing population it is not uncommon for people to experience quite significant fatigue low motivation and foggy thinking in the initial period- leading many to consider discontinuing; you need to have a plan and approach to push through that if it happens as the benefits all happen on the other side.

• Interesting. My N1 experience on a two month cycle of Tirzepatide was 2.5 mg fine to start, but wouldn’t I wanted to have stayed at it, nor go any higher than 5mg due to over appetite suppression. So far maintaining fairly well …but I’m only two weeks out after completing two months cycle of 2.5 followed by 5 mg weekly.

• Why not just stay at 2.5 mg?

• Not sure if this is addressed to me, but it was simply not an adequate level of effect. The RCT data bear is out that I’m not alone. As far as I’m concerned, though, the mass majority of affect is at 5 mg and if someone had excellent affected 2.5, I would not push the dose higher. Lowest effective dose.

• The plan being: not skipping meals, high protein/fiber, ensuring adequate hydration

  ??

• “Skipping meals“ is not clear. One should not eat simply because of “meal time“. One should eat when hungry (not saying waiting until starving but reasonably hungry) stop when comfortably (versus uncomfortably) full, or we no longer hungry. I think we do a disservice to patients by telling them they have to eat at times outside of biological drive.

• I’ve seen good use of tirzepatide low dose for use around holidays and in winter only

• I thought microdosing of tirzepatide was something like .5 mg weekly … or even less. That said … is anyone doing that? How has that worked out?

  I’m still on the fence with these meds as I was severely burned in the past by Phen-fen, lap banding, and numerous other surgical devices for GYN surgery and many prior blockbuster pharmaceuticals … as I’ve been in practice a long time … and fear long term complications and lack of long term compliance … with resulting worsening of metabolic health.

  I want to research all that can more naturally improve mitochondrial function long term - I want to learn more about this quantum research … and good old lifestyle and hormones are truly great for creating healthy peptides!!

  I’m still sticking to the “low lying fruit” for my personal healthy longevity plan! Lifestyle medicine isn’t easy medicine!! Nothing like a magical shot … but I’m so jaded that I ceased to believe in “magical thinking” as regards health.

  So far … so good for me!!

  But I love learning from all of you and I truly do have a wide open mind. Something “magical” does still entice!

  My 2025 resolution is to try to stay on top of these many texts!!

• “Interestingly, the dual GIP/GLP-1 receptor activating drug tirzepatide has an amino acid sequence with strong parallels to the native GIP sequence, and subsequently exhibits preference for GIP over GLP-1 receptor binding. In this regard, tirzepatide may offer an exciting new option for improving bone health ….

  “Accordingly, bariatric surgeries that are considered gold-standard to manage obesity have been associated with increased bone fracture risk…”

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10938612/

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🩺 Publications

Disagreement on foundational principles of biological aging

A survey of aging researchers revealed no consensus on key questions like the definition, causes, and onset of aging, leading to varied research priorities. Clearer definitions and unified goals are needed to address critical unanswered questions and advance the field.

PNAS Nexus- Recommended by Dr. David Luu

Cellular and Mitochondrial NAD Homeostasis in Health and Disease

This review explores the critical role of NAD in mitochondrial energy metabolism, detailing its synthesis, degradation, transport, and subcellular localization. It highlights how pathological depletion of mitochondrial NAD impacts protein modifications and contributes to neurodegeneration, emphasizing the importance of understanding NAD dynamics for health and disease.

Cells - Recommended by Dr. Desmond Ebanks

Physical Activity and All-Cause Mortality by Age in 4 Multinational Megacohorts

In this pooled analysis of cohort studies, the association between PA and mortality risk remained consistent across the adult lifespan, which contrasts with other modifiable health factors, for which associations with mortality risk diminished with age. Given these findings, the promotion of regular PA is essential at all stages of adult life.

JAMA Network - Recommended by Dr. Giovanni Campanile

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🌐 In the Media

• The Allure of Ozempic microdosing

• Do ‘Blue Zones’ rest on shaky science?

• Why aging experts are obbessed about healthspan?

• Nerve fibres in the brain could generate quantum entanglement

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🗓️ Upcoming Events

• Longevity Docs Meetups

  • San Francisco: December 8

  • Los Angeles: December 10

  • Montecito: December 11

  • Las Vegas: December 14

  • New York: December 17

  • Cannes, France: June 24-26, 2025

• A4M Fest - December 13-15, Las Vegas

• Founders Longevity Forum - Singapore, February 27-28, 2025

• The Longevity Med Summit - Lisbon, May 6-8, 2025

• Life Summit - Berlin, May 27-28, 2025

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🚀 5 Reasons to Join Longevity Docs

1. Join a Trusted Network of Leaders
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2. Access Unparalleled Events and Insights
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3. Lead the Way in Research and Innovation
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4. Elevate Your Practice and Knowledge
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5. Shape the Future of Longevity Medicine
   Collaborate with peers to build the future of healthcare, making longevity medicine more effective, accessible, and impactful for patients worldwide.

⚡ Join Now: Together, We’re Redefining Medicine. Be part of a global network making a difference—apply today!

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Newsletter Disclaimer:

The content shared in this newsletter, including the "Buzz in the Chat" section, is for educational purposes only. It is derived from peer-to-peer conversations among physicians within the Longevity Docs community and is intended to inform and engage our network of doctors.

Please note that these discussions do not reflect the official position of Longevity Docs and are not to be interpreted as medical advice or recommendations. The insights and opinions shared are those of individual physicians and are provided as part of our mission to foster collaborative learning and dialogue among healthcare professionals.

We encourage all readers to consult qualified healthcare professionals for personalized medical advice and to evaluate any medical information in the context of their clinical expertise and patient needs.

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