What Supplements Have You Tried to Slow Aging?
In the world of anti-aging, it’s common to see biohackers downing dozens—or even hundreds—of supplements a day. It often seems like longevity depends on rows of pill bottles. But does it really have to be this way?
A new study from Tsinghua University may upend that assumption. Researchers have developed an “anti-aging vaccine” that offers benefits even long-term NAD+ supplementation has failed to achieve.
The NAD+ Leak Behind Aging: CD38’s Hidden Role
NAD+ is a vital energy molecule that keeps every cell in our body functioning youthfully. But its levels steadily decline with age. A major culprit? An enzyme called CD38.
CD38 is a membrane-bound protein found mostly on immune cells like lymphocytes and macrophages, especially concentrated in the bone marrow and lymphoid tissues. It breaks down NAD+ into other molecules and activates NAD+-dependent enzymes such as the SIRT family, which defend against oxidative stress. While CD38’s activity is modest in youth, it becomes overactive with age—consuming NAD+ rapidly and contributing to mitochondrial dysfunction.
This explains why simply supplementing NAD+ precursors like NMN or NR doesn’t always yield expected results. If NAD+ is your body’s “energy tank,” CD38 is the leak at the bottom. You can’t solve the problem by just pouring in more.
A New Strategy: Vaccinating Against CD38
Instead of developing another CD38 inhibitor, researchers took a novel approach—designing a vaccine.
They identified a unique peptide on CD38 (ANYEFSQV) and fused it with KLH (a common vaccine carrier protein), adding aluminum adjuvant to stimulate an immune response. The result? A CD38 peptide vaccine that trains the immune system to recognize and eliminate cells that express CD38 excessively—plugging the NAD+ “leak” at its source.
Promising Results: Better Strength, Memory, and Metabolism
Using a “prime-boost” vaccination schedule (initial shot at 12 months of age in mice, booster at 18 months), researchers observed notable improvements:
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Targeted immune activation: The vaccine stimulated a Th1-type immune response, promoting precise clearance of CD38+ myeloid cells from the spleen and liver.
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Improved physical performance: Vaccinated mice showed stronger grip, longer running time, and better endurance.
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Enhanced cognitive function: They displayed better spatial learning, memory, and curiosity.
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Metabolic benefits: Glucose tolerance, insulin sensitivity, and oxygen consumption all improved.
At the molecular level, NAD+/NADH ratios increased in the liver and brain, senescence markers (like IL-6 and P21) were reduced, and energy-related proteins were upregulated while glycolytic proteins were downregulated.
Anti-Aging Vaccines vs. Other CD38 Inhibitors
Other CD38-targeting compounds include:
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Natural flavonoids like apigenin and quercetin.
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78c, a small-molecule inhibitor with lifespan-extending effects in mice (~10%).
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Monoclonal antibodies like daratumumab (used in multiple myeloma), though its side effects make it unsuitable for anti-aging purposes.
In contrast, vaccines could offer a long-lasting, self-sustaining solution via the body’s own immune system—without daily pill routines.
The Broader Landscape of Anti-Aging Vaccines
While CD38 vaccines are promising, they’re not alone. Alzheimer’s vaccine candidates (e.g., ALZ-101, ACI-24, ABvac40) targeting amyloid-beta or tau are already in clinical trials, though large-scale breakthroughs are pending.
Other anti-aging vaccine efforts include:
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GPNMB-targeting vaccines (Juntendo University) for atherosclerosis and metabolism.
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CD153-targeting vaccines (Osaka University) to reduce senescent T cells and improve glucose handling.
Challenges Ahead
Despite exciting early data, questions remain: How long do the effects last? What are the side effects? What’s the optimal dose and frequency? And how scalable are these vaccines?
Still, this marks an inspiring new frontier. With fewer pills and more immune precision, anti-aging might soon become simpler—and smarter.
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