Masterclass on SGLT-2 • 1-MNA Effects in Cancer • Ageing as a Mindset • SF Meetup
Your sneak peek into the world of Longevity Docs.
Hey Docs - Welcome to the Longevity Docs Newsletter—your pulse on the latest in longevity medicine. This week, Dr. Elizabeth Yurth takes us deep into the science of 1MNA, while Dr. Nicole Sirotin and Dr. Andrea Maier set a global benchmark with the launch of longevity clinic guidelines in Abu Dhabi.
A special thank you to Abid Hussain will share his expertise on SGLT2 inhibitors in our Masterclass.
Don’t miss our San Francisco meetup on December 6, a unique moment to connect and exchange insights with other Longevity Docs.
And as always, keep the longevity mindset sharp and focused.
Happy Sunday!
Dr. David Luu
This Week:
Community
Weekly Pulse Updates
Meet nine new Longevity Docs
Masterclass: SGLT2 Inhibitors - The Longevity Promise with Dr. Abid Husain
Buzz in the chat: 1-MNA Effects in Cancer
Research:
Antidiabetic Medication and Asthma Attacks
Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men
Ageing as a mindset
In the News
What Longevity clinics can learn from Forward Health's closure
👋 Community
Weekly Pulse Updates
New Longevity Docs' Intro
San Francisco Meetup
The Longevity Docs Meetup is more than just an event—it’s your chance to connect with a community that gets it. We know how hard it is to push boundaries, stay on top of the latest science, and grow your practice.
That’s why we’re bringing together the top longevity physicians in San Francisco to share insights, ideas, and inspiration in an intimate, exclusive setting.
🎓 Masterclass
SGLT2 Inhibitors - The Longevity Promise with Dr. Abid Husain
Join us for a 60-minute masterclass with Dr. Abid Husain, a leading cardiologist and expert in longevity medicine, as he delves into the transformative potential of SGLT2 inhibitors. Originally developed for diabetes management, these innovative medications are now gaining attention for their remarkable benefits in heart and kidney health, and their exciting potential to enhance healthspan.
Don’t miss this opportunity to learn from one of the field’s top experts!
💬 Buzz in the Chat
1-MNA Effects in Cancer (by Dr. Elizabeth Yurth)
1-methylnicotinamide (1-MNA) has complex and seemingly paradoxical effects on cancer depending on whether it's studied in vitro (in cell cultures) or in vivo (in living organisms).
In Vitro (Cell Culture Studies):
Acts as a methyl donor, promoting DNA methylation.
Can increase cancer cell proliferation and enhance metabolic activity.
May upregulate pro-growth signaling pathways.
In Vivo (Whole Organism Studies):
Exhibits anti-angiogenic properties, preventing new tumor blood vessel formation.
Displays anti-inflammatory effects, limiting tumor growth and spread.
Enhances immune recognition and response to cancer cells.
Normalizes blood vessels, improving chemotherapy drug delivery.
Mechanisms of NNMT and 1-MNA
NNMT and 1-MNA Interplay:
1-MNA is a product of NNMT-catalyzed reactions and inhibits NNMT through feedback inhibition.
NNMT overexpression correlates with disease states like cancer, metabolic disorders, and neurodegenerative diseases.
Excessive NNMT activity drains methyl donors (SAM), leading to DNA/histone demethylation and upregulation of tumor-associated genes.
Elevated NNMT depletes mitochondrial NAD+, disrupting cellular metabolism and function.
1-MNA Regulation:
1-MNA prevents excessive pyridone (2PY, 4PY) production, maintaining physiological balance.
Self-regulatory mechanisms enable 1-MNA to inhibit NNMT and restore NAD+ levels under energy-consuming states (e.g., aging, cancer).
Pyridone Pathways and Metabolism
Niacin supplementation leads to higher pyridone production compared to 1-MNA, potentially exceeding safe thresholds.
Hormetic levels of 2PY metabolites support cellular repair, exhibiting anti-inflammatory and anti-fibrotic effects.
NAD+ precursors (e.g., NR, NMN) also raise pyridone levels but at a faster rate than 1-MNA.
Clinical Implications
NNMT overexpression correlates with disease but does not directly cause it; 1-MNA levels rise in response to increased NNMT as part of a regulatory feedback loop.
Elevated 1-MNA in diseases like cancer should be interpreted as a correlation, not causation, pointing to underlying metabolic dysfunction.
Key Takeaways
Complex Role of 1-MNA in Cancer:
Effects differ between isolated cell environments (in vitro) and living systems (in vivo), with the latter showing therapeutic potential.
NNMT as a Therapeutic Target:
Overexpressed NNMT disrupts cellular homeostasis, making it a promising target in treating cancer and metabolic diseases.
Self-Regulating Mechanism of 1-MNA:
Balances NNMT activity and NAD+ levels, minimizing harmful pyridone production and restoring cellular function.
Niacin vs. 1-MNA:
High doses of niacin increase pyridone production, potentially leading to toxic levels, whereas 1-MNA stays within safe physiological limits.
Correlation ≠ Causation:
Elevated 1-MNA levels are a response to NNMT upregulation, not a direct cause of disease.
Research Opportunities:
Expanding studies on NNMT and its inhibitors could uncover novel treatments for diseases linked to metabolic dysfunction.
🩺 Publications
Antidiabetic Medication and Asthma Attacks
A new study explored whether metformin and GLP-1 receptor agonists (GLP-1RAs), diabetes medications, can reduce asthma attacks. Using data from over 12,000 patients, metformin lowered asthma attack risk by 30%, with GLP-1RAs adding an additional 40% reduction. Results were consistent regardless of glycemic control, weight, or asthma type. While observational, these findings suggest repurposing these medications as alternative asthma treatments, warranting further clinical trials.
JAMA Internal Medicine - Recommended by Dr. Neil Paulvin
Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men
This study explored the associations of circulating testosterone (T) and sex hormone-binding globulin (SHBG) with fracture risk in men, using data from the UK Biobank cohort (n = 205,973). Lower SHBG was strongly associated with reduced fracture risk across all bone sites, while the relationship between T and fractures was weaker, nonlinear, and inconsistent among sites. Findings suggest SHBG is a stronger independent biomarker of fracture risk than T. Limitations include potential residual confounding and reliance on a single cohort, limiting generalizability.
JCEM - Recommended by Dr. Desmond Ebanks
Ageing as a mindset: a study protocol to rejuvenate older adults with a counterclockwise psychological intervention
The research aims to investigate whether changing age-related mindsets through a "counterclockwise" intervention can alter physical, cognitive, and psychological aspects of ageing. The study could revolutionize perceptions of ageing, suggesting that mindset and psychological interventions can improve health outcomes and reduce age-related decline.
BMJ - Recommended by Dr. Olivia Lesslar
🌐 In the News
New clinic guidelines to set global standards in longevity medicine
Abu Dhabi has partnered with IHLAD and HLMS to launch the world’s first evidence-based clinical guidelines for healthy longevity medicine. These standards, effective April 2025, redefine healthcare with a focus on prevention, advanced diagnostics, and personalized interventions to support healthy aging.
🗓️ Events & conferences
Longevity Docs Events
Longevity Docs Meetup - December 6, San Francisco
Longevity Docs Cannes: Cannes, France - June 24-26, 2025
Other events
Longevity Summit - December 3-4, Novato
Roundtable of Longevity Clinics - December 6-7, Novato
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