Mr. William 🧬🦎

Scientist at Geroprotect® Open-source longevity supps. Natural small molecules & peptides. Chemical reprogramming, biohacking, biochem engineering.

[Dalton (Analyze & Optimize) @Outdoctrination]

Natural anti-inflammatories, and what diseases they're relevant for:

◇ Vitamin D ➜ ↓ IL-17, ↓ IL-23, ↑ Tregs ➜ Multiple sclerosis, psoriasis, Crohn's disease
◇ Curcumin ➜ ↓ IL-23/Th17 signaling ➜ Ulcerative colitis, Crohn's disease, psoriasis
◇ Butyrate ➜ ↑ IL-10, ↑ Tregs, ↓ IL-23/IL-17 axis ➜ Ulcerative colitis, Crohn's disease
◇ Lactobacillus reuteri ➜ ↑ IL-10, ↑ Tregs ➜ Atopic dermatitis, ulcerative colitis
◇ Omega-3 (EPA/DHA) ➜ ↓ IL-17, ↓ IL-23, ↓ TNF-α ➜ Rheumatoid arthritis, psoriasis
◇ Sulforaphane ➜ ↓ IL-17, ↓ IL-23 (via NF-κB and Nrf2 modulation) ➜ Psoriasis, autoimmune disease
◇ Resveratrol ➜ ↓ IL-17, ↓ Th17 differentiation ➜ Multiple sclerosis, rheumatoid arthritis
◇ Quercetin ➜ ↓ IL-17, ↓ IL-4 ➜ Asthma, allergic disease
◇ Melatonin ➜ ↓ NLRP3 inflammasome ➜ ↓ IL-1β ➜ Gout, recurrent pericarditis, autoinflammatory syndromes
◇ Berberine ➜ ↓ NLRP3 inflammasome, ↓ IL-1β ➜ Type 2 diabetes, NAFLD
◇ Vitamin D ➜ ↓ IFN-γ, ↑ Tregs ➜ Multiple sclerosis, type 1 diabetes
◇ Curcumin ➜ ↓ IFN-γ ➜ Rheumatoid arthritis, Crohn's disease
◇ Boswellia serrata ➜ ↓ Leukotrienes (5-LOX) ➜ Asthma, ulcerative colitis

[Shawn Wells @Ingredientology]

Fisetin and apigenin are two flavonoids being studied for their potential benefits in healthy aging and cellular resilience.

Potential benefits:

-may help clear senescent “zombie” cells
-support mitochondrial energy production
-help regulate inflammation and oxidative stress
-support brain and cognitive health
-may support metabolic function and healthy aging pathways

Fisetin is found in strawberries and apples.
Apigenin is found in parsley, chamomile, and celery.

[Jesse Morse, M.D. @DrJesseMorse]

https://t.co/EPU7XU6ZTC

[Agingdoc🩺Dr David Barzilai🔔MD PhD MS MBA DipABLM @agingdoc1]

Urolithin A: A Novel Postbiotic for inflammation, aging, and cancer: A Journey from Dietary ellagitannins to clinical use

https://t.co/CLWoHQXZbu

[Jake Gilman @jakeglmn]

Everyone from Joe Rogan to the Kardashians swears by NAD for anti-aging and recovery.

Rhonda Patrick interviewed the scientist who discovered the molecule behind it.

Dr. Charles Brenner.

Here's everything you need to know (thread):

1) NAD fixes damaged DNA

[Mr. William 🧬🦎 @1313geroprotect]

Levin’s work becomes increasingly important as you move toward systemic, in-vivo rejuvenation much like the overlap with Picard on metabolic/energy transitions. Chemical reprogramming can drive cells into hybrid E/M states, and those states are metabolically incoherent and prone to lipid peroxidation and lipotoxicity (ferroptosis vulnerability via PUFA-enriched membranes). Cells need guidance and direction. There has to be coherence.

[Mr. William 🧬🦎 @1313geroprotect]

I don’t think chemical reprogramming or bioelectricity has anything to do with micromanaging. Micromanaging isn’t even possible here just look at the epigenetic, metabolic, and immunogenic load running in parallel. Think about the energy cost of the metabolic transition alone; there’s so much happening inside the cell at once that it’s remarkable Deng gets CiPS in 10 days, from multiple donors, at high efficiency.
He’s touching a handful of nodes that’s it. Same with Levin: a few nodes, five chemicals and a bioelectric state, and non-regenerative animals start to regenerate. Both are touching very little and unleashing enormous downstream self-organization. That’s the opposite of micromanaging you set a few upstream conditions and the cell’s own intelligence does the rest.
Read the two side by side and the overlap is striking. Compared to OSK, a genuinely blunt tool, this targeted approach has, in my view, a far higher ceiling. And underneath all of it: aging is a loss of regeneration.

[Mr. William 🧬🦎 @1313geroprotect]

10-day human chemical reprogramming, all donors — Nat Chem Biol 2025 (PMID 39753706)
• From peripheral blood — Cell Discovery 2025
• Autologous CiPSC islets → insulin independence in a T1D patient — Cell 2024 (PMID 39326417)
• XEN-like → regeneration program (MSX1/2, HOXB9, SALL4, blastema-like) — Nature 2022 (Guan/Deng)
• Adult frog limb from a 24h cocktail — Murugan, Sci Adv 2022

Most important papers related to this subject. But there are many more.

[Master Metabolism @lowmegatron]

New Hashimoto's research shows that near infrared light crushes anxiety, depression, fatigue, pain, and sleep problems in Hashimoto’s hypothyroidism in 3 weeks.

The patients were all still suffering on levothyroxine. 🧵

[Dalton (Analyze & Optimize) @Outdoctrination]

Hydrogen water successfully treated chronic fatigue.

Series of case reports - multiple people with ME/CFS given molecular hydrogen inhalation therapy.

All reported improvements in energy + brain fog, as well as headache.

Hydrogen works primarily by detoxifying the most damaging free radical in our body (OH radical) - allowing for more effective energy generation + lower inflammation.

[Charles Brenner, PhD @CharlesMBrenner]

@Peter_1_1 NR is the most effective intervention ever tried in peripheral artery dz and has 8 RCTs showing lower inflammatory markers in humans

if you are looking for the bro who said take NMN & resveratrol so you'll never age, it's someone else

[Aging Science News @AgingBiology]

Resveratrol isomers with opposing activities target endonuclease G to modulate neurodegeneration and mitochondrial elimination
https://t.co/idBgyBUO7m

[Mr. William 🧬🦎 @1313geroprotect]

@Outdoctrination It’s just business don’t take it personal

[Dalton (Analyze & Optimize) @Outdoctrination]

The benefits of RED / NEAR INFRARED LIGHT for the brain are amazing.

➟ Enhances brain connectivity
➟ Supports glymphatic clearance
➟ Increases BDNF
➟ Reduces Alzheimer's plaque accumulation (animals)
➟ Improves cognition
➟ Enhances stroke recovery
➟ Preserves dopamine producing neurons (animals)
➟ Promise in Parkinson's
➟ Aids in healing TBI / concussion / CTE
➟ Anti-depressant
➟ Anti-anxiety

Thanks to its ability to enhance mitochondrial energy metabolism + stabilize intracellular water structure.

[Agingdoc🩺Dr David Barzilai🔔MD PhD MS MBA DipABLM @agingdoc1]

Ergothioneine as a potential geroprotector: Targeting molecular hallmarks of ageing and age-related diseases

https://t.co/KdVoWNQ4He

[Mr. William 🧬🦎 @1313geroprotect]

@agingdoc1 Glucosamine drives pro-EMT aging pathways like YAP/TAZ. It’s useful, but I don’t consider these kinds of supplements healthy for everyone.

The same goes for collagen peptides, glutamine, and a lot of the fitness category: protein, arachidonic acid, and phosphatidic acid.

[Mr. William 🧬🦎 @1313geroprotect]

Viral vectors are a blunt tool, integration risk, forced oncogenes, crude control. Chemical reprogramming, done in vivo, is far more sophisticated: small molecules that tune cell state precisely, no transgenes.

In China, Deng Hongkui’s labs have cut human reprogramming to as little as 10 days, reproducibly across every donor tested, and shown robust induction straight from peripheral blood. That same chemical platform already put a type-1 diabetic into insulin independence with their own CiPSC-derived islets. That’s where China’s new stem-cell trials are coming from and it’s moving fast.

What excites me most: the chemical route passes through a XEN-like / intermediate plastic state that reactivates the exact regeneration program of axolotl limb regeneration and the human limb bud, MSX1/2, HOXB9, SALL4. Viral OSKM never touches this. It’s unique to chemistry.

And this is exactly where Levin’s work bites. His Tufts team regrew a functional hind leg in adult frogs, animals that, like us, have lost the ability to regenerate, from a single 24-hour hit of a five-drug cocktail under a wearable “BioDome.” One day of signal, 18 months of regrowth: bone, nerves, vasculature, muscle, with sensation and movement restored (Murugan et al., Sci Adv 2022).

His point is the one that matters for in vivo reprogramming: you don’t micromanage the limb, the morphogenetic blueprint is still resident in the adult body. You trigger the blastema and let the bioelectric pattern do the building. Chemistry reopens the regeneration program; bioelectricity tells it what to build and when to stop.

That blastema-like state is a far more interesting in-vivo target than plain partial reprogramming. I think it preferentially engages damaged cells and tissue, and on telomeres and epigenetic age it sits further down the rejuvenation axis than a partially reprogrammed cell.

With autologous stem cells, this speed, and this technology, I have no doubt longevity escape velocity gets reached on their side well before ours.

[Mr. William 🧬🦎 @1313geroprotect]

Aging isn't a one-way street. Partial cellular reprogramming + the right small molecules and peptides are rewriting the clock — open-source, no $2M budget required. 🧬🦎

[Mr. William 🧬🦎 @1313geroprotect]

@johnhemming4mp @CharlesMBrenner It blunts exercise performance, shifts to glycolysis, damages the gut lining….

[Daniel Tawfik @dantawfik]

Urolithin A alone reduced Alzheimer's pathology across multiple markers in a new preclinical study. Combined with EGCG, it produced effects two to four times larger across most measures—and for one critical synaptic protein, the combination increased expression more than seven times as much as urolithin A could achieve independently.

This isn't addition. It's synergy.

The mechanistic logic explains why. Urolithin A and EGCG work through complementary pathways that address different points in the Alzheimer's disease cascade. Urolithin A enhances mitophagy—the cellular quality control system that clears damaged mitochondria before their dysfunction compounds. It also shifts mitochondrial networks toward the more connected, tubular morphology associated with efficient energy production.

EGCG works upstream and downstream of that. It redirects amyloid-beta away from toxic aggregate forms, converts existing fibrils into less harmful structures, suppresses chronic microglial inflammation, and enhances tau clearance. Where urolithin A restores the machinery that clears amyloid, EGCG reduces the amyloid and inflammatory burden actively undermining what urolithin A is trying to restore.

One repairs the system. The other reduces the load on it.

When researchers tested both compounds in a mouse model of late-onset Alzheimer's disease, the combination consistently outperformed urolithin A alone across behavioral, molecular, and structural measures.

Mitochondrial fragmentation—the hallmark structural dysfunction in Alzheimer's—was corrected by urolithin A. The combination amplified that correction dramatically. Proteins driving fragmentation were suppressed. Proteins promoting fusion and healthy connectivity were elevated. Effect sizes for the combination were roughly two to four times larger than urolithin A alone across most mitochondrial dynamics markers.

One fusion protein showed a particularly striking difference—increasing more than four times as much with the combination as with urolithin A alone.

Mitochondrial function followed the same pattern. Oxidative stress fell further with the combination. Membrane lipid peroxidation fell further. ATP production rose higher. The mitochondria in combination-treated mice were running cleaner and producing more usable energy than urolithin A could achieve independently.

That functional improvement created the conditions for synaptic restoration—and this is where the most dramatic amplification appeared.

Synaptic gene expression showed some of the largest differential responses in the dataset. One key synaptic protein increased more than seven times as much with the combination as with urolithin A alone. Several others showed similarly amplified effects. These aren't marginal differences. They're qualitatively different responses suggesting the combination is engaging repair pathways that urolithin A alone cannot fully activate.

The physical structure of synaptic connections—measured directly through dendritic spine density and length—improved in both treatment groups, but the combination produced broader restoration across brain regions than urolithin A could achieve independently. Synapses are the microscopic structures through which memory is encoded and retrieved. Their restoration is the structural correlate of the cognitive improvements measured behaviorally.

Amyloid levels fell in both groups, with the combination producing the larger reduction. Both major forms of amyloid-beta that accumulate in Alzheimer's were reduced. This is the result the metabolic hypothesis predicts: restore mitochondrial function and the energy-dependent clearance machinery that processes amyloid, reduce the inflammatory environment that impairs that clearance, and amyloid falls as a downstream consequence.

The convergence matters. The intervention didn't just move one marker. It improved mitochondrial morphology, reduced oxidative damage, increased energy output, restored synaptic structure, reduced neuroinflammation, and lowered amyloid burden. That breadth across mechanistically distinct outcomes is consistent with correcting upstream metabolic failures rather than modulating a single downstream target.

Most drug development focuses on optimizing single compounds against single targets. This study suggests the intervention structure for complex neurodegenerative diseases may need to be fundamentally different—combinations that address multiple points in the cascade simultaneously rather than betting everything on one mechanism.

Urolithin A restores mitochondrial quality control. EGCG reduces the pathological load and inflammatory environment. Together they produce effects neither can achieve alone.

The distance between mouse models and human clinical outcomes remains real. Pharmacokinetics differ. Blood-brain barrier penetration varies. Dosing and timing matter. The simple fact that mice are not humans means positive preclinical data does not guarantee human efficacy.

But the mechanistic rationale is sound. Mitophagy declines with age. Mitochondrial dysfunction appears early in Alzheimer's pathology, often before plaques accumulate. Energy-dependent clearance systems fail when cellular energy supply collapses. Neuroinflammation compounds the dysfunction. Addressing multiple upstream failures simultaneously could plausibly interrupt the cascade before irreversible damage occurs.

Urolithin A and EGCG are not experimental drugs awaiting regulatory approval. They're naturally occurring compounds with well-established safety profiles, available as supplements—though bioavailability and gut microbiome variation mean not everyone produces or absorbs them equally.

The decisions about whether to intervene metabolically before clinical dysfunction appears—and whether to use combinations rather than single compounds—depend on understanding which upstream failures drive the downstream pathology and whether simultaneous restoration can prevent progression in humans.

This study suggests combination therapy may be the structure, not just the strategy.