Butyrate: The Microbiome's Anti-Aging "Kill Switch" for Senescent Cells

Thank you @RapAdmin - going to give this a try. $50. Why not. Here is what I am doing:

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Could you add to your prompt and post “What is the easiest and most accurate way to measure the results of doing this protocol?” - Or, something like that. Thank you!

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That is clostridium butyricum but I’m pretty sure not the strains found in the dirt in Japan which is the proven one.

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There are also the Galacto-Oligosaccharides which are effective at low dose and produce comparatively less gas (their take).

Open Acess paper: Galacto-Oligosaccharides Exert Bifidogenic Effects at Capsule-Compatible Ultra-Low Doses


Figure 3 GOS boosted SCFA production in a dose-related manner, which was accompanied by only mild increases in gas production. The impact on (A) total SCFA (mM), (B) gas production (mbar), and (C) the ratio of gas being produced per mole of SCFA.


Figure 4 GOS boosted production of the three main SCFAs and lactate in a dose-related manner. The impact on (A) acetate (mM), (B) lactate (mM), (C) propionate (mM), and (D) butyrate (mM).


Figure 5 GOS exerted significant bifidogenic effects from the lowest dose onwards, relating to enhanced acetate and butyrate production. Average level (cells/mL) of (A) microbial phyla and (B) Bifidobacteriaceae (main family within Actinomycetota; deconvoluted in its main OTUs) (n = 8), along with correlations of absolute Bifidobacteriaceae levels with (C) acetate and (D) butyrate.


Figure 6 GOS significantly stimulated Lachnospiraceae members from the lowest test dose onwards, relating to enhanced acetate and butyrate production. Average level (cells/mL) of (A) Lachnospiraceae (main family within Bacillota_A; deconvoluted in its main OTUs) (n = 8), along with correlations of absolute Lachnospiraceae levels with (B) acetate and (C) butyrate.

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Good find. Yes - it sounds good.

More information:

Galacto-Oligosaccharides (GOS) are non-digestible carbohydrates composed of chains of galactose units. They are widely recognized as one of the most effective “bifidogenic” prebiotics available. Unlike inulin or FOS (Fructo-Oligosaccharides), which are fermented broadly, GOS has a high specificity for stimulating Bifidobacterium species in the human gut.

1. Mechanism of Action

  • Resistance to Digestion: GOS resists hydrolysis by human salivary and pancreatic enzymes (amylases) due to their β-glycosidic linkages. They reach the colon largely intact.
  • Selective Fermentation: In the cecum and proximal colon, GOS are selectively fermented by Bifidobacterium and Lactobacillus species. These bacteria possess specific β-galactosidase enzymes required to break down GOS.
  • SCFA Production: The fermentation of GOS results in the production of Short-Chain Fatty Acids (SCFAs) and gases (H2​, CO2​).
    • Acetate: The primary SCFA produced by Bifidobacteria via the “bifid shunt.” It is the most abundant SCFA in the blood and supports muscle and heart tissue energy.
    • Butyrate: Produced through cross-feeding. Bifidobacteria degrade GOS into acetate and lactate, which are then utilized by butyrate-producing species (e.g., Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia) to generate butyrate. Butyrate is the preferred energy source for colonocytes (gut lining cells) and is crucial for maintaining the gut barrier and regulating inflammation.
    • Propionate: Produced in smaller quantities, involved in hepatic gluconeogenesis and satiety signaling.

2. Clinical Evidence

  • Bifidogenic Effect: Numerous Randomized Controlled Trials (RCTs) confirm that GOS doses of 2.5g to 5g/daysignificantly increase fecal Bifidobacterium counts in healthy adults, infants, and the elderly.

  • Symptom Management:

    • IBS: GOS is generally better tolerated than Inulin/FOS, producing less gas/bloating at equivalent effective doses.
    • Constipation: Evidence supports GOS increasing stool frequency and softening stool consistency, particularly in the elderly.
    • Anxiety/Mood: Emerging evidence (e.g., Schmidt et al., 2015) suggests GOS may attenuate the waking cortisol response and improve anxiety, likely via the gut-brain axis modulated by SCFAs.

3. Limitations & Debates

  • Dosage Threshold: While 2.5g is effective, higher doses (>10-15g) can cause osmotic diarrhea and flatulence.
  • Individual Variability: The “cross-feeding” effect relies on the presence of resident butyrate producers. If a user lacks F. prausnitzii, GOS alone may not maximize butyrate production compared to direct butyrate supplements, though it will still drive Acetate.

Top Cost-Effective Brands of Galacto-Oligosaccharides (GOS)

Market Note: Unlike Inulin or Psyllium, pure GOS is difficult to find as a standalone bulk powder in the consumer market. It is most frequently sold as a branded prebiotic blend or a high-end specific supplement (e.g., Bimuno).

The table below identifies the top consumer-accessible sources, ranked by Value (Cost per 100g). Prices are estimated based on current retail data and may fluctuate.

Rank Brand Product Name Form GOS Content Cost / 100g (Approx)
1 Natural Chemist Galacto-oligosaccharide (GOS) Powder Powder ~80% Pure GOS $22.00
2 Bimuno Daily Prebiotic Supplement (Powder) Powder High (B-GOS) $35.00*
3 Invivo Bio.Me Prebio GOS Powder Pure GOS $37.00
4 Klaire Labs Galactomune Prebiotic Powder GOS + Beta-Glucan $38.00
5 Microbiome Labs MegaPre Powder GOS + FOS + XOS $41.00
6 Moss Nutrition Select GOS (GI Select) Powder Pure GOS $45.00
7 Swanson Prebiotic GOS (Discontinued/Rare) Caps Varies N/A (Market Gap)
8 Vitalus Vitagos (Ingredient Source) Bulk Pure GOS Wholesale
9 Liposomals Prebiotic GOS Liquid GOS Syrup $48.00
10 ProThera Galactomune Powder Same as Klaire Labs $50.00

*Note on Bimuno: Calculated based on the 90-sachet bulk pack price (~£90 / ~$115 USD for 328g). Small trial packs are significantly more expensive per 100g (~$113/100g).

Practical Insight: If you cannot find a pure GOS product locally, look for “Prebiotic Blends” that list Galacto-oligosaccharides as the first ingredient. Avoid products that label themselves “Prebiotic” but only contain Inulin (Chicory Root) or FOS, as these are cheaper and less specific for Bifidobacteria.

I had a similar experience. I had IBS-D since teenager years. I initially mostly managed it with low FODMAP diet. But in the past 1-2 years I managed a full remission with green-med diet that includes about 60-80 grams of fiber a day - all dietary sourced. I was able to reintroduce most of the FODMAPS although I still stay away from added inulin and garlic powder.

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They are talking about butyrate and more of the miracles it participates in. I think my CB must be coming all the way from Japan it’s taking forever.

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Gemini AI Video Summary:

Executive Summary

This transcript features a technical dialogue between a host and Dr. Zain Kassam, a gastroenterologist and biotechnology expert, regarding the intersection of the gut microbiome, metabolic health, and body composition. The conversation moves beyond the antiquated “Firmicutes/Bacteroidetes ratio” to focus on mechanistic pathways, specifically identifying butyrate as a master signaling molecule.

The primary thesis is that the gut microbiome functions as a metabolic organ that modulates host energy harvest, insulin sensitivity, and appetite through secondary metabolites. Dr. Kassam highlights seminal research where fecal microbiota transplants (FMT) from lean donors into obese mice—and later humans with metabolic syndrome—transferred phenotypic traits like leanness and improved insulin sensitivity. He posits that the efficacy of these shifts is increasingly linked to the stimulation of intestinal GLP-1 (glucagon-like peptide-1) via the gut’s L-cells, which signal the vagus nerve to increase satiety.

Furthermore, the discussion explores the “gut-muscle axis,” referencing data that suggests certain microbial profiles are associated with higher physical function in the elderly. Mechanisms proposed include optimized protein breakdown (anabolism) and the suppression of systemic inflammation (catabolism). A notable highlight is the identification of Veillonella in elite athletes, a bacteria that metabolizes lactic acid into propionate, potentially enhancing endurance performance.

Dr. Kassam concludes by emphasizing the clinical importance of cross-feeding. He argues that the microbiome is an interdependent ecosystem where “bystander” bacteria must first process fiber into intermediate metabolites before butyrate-producing organisms can function. For those seeking actionable longevity benefits, the focus should be on dietary diversity and specific prebiotics (inulin, pectin) to fuel this butyrate factory, thereby reducing low-grade chronic inflammation and optimizing metabolic substrate switching.


Bullet Summary

  • Fecal Transplants & Phenotype: Early studies demonstrated that transferring stool from obese vs. lean human twins into germ-free mice successfully transferred the corresponding weight phenotype.
  • Insulin Sensitivity: FMT from healthy donors into humans with metabolic syndrome significantly improved insulin sensitivity, though direct weight loss results remain maturing.
  • Obsolete Metrics: The Firmicutes to Bacteroidetes ratio is no longer considered a reliable hallmark for obesity due to high variability and confounding factors.
  • Butyrate as Master Regulator: Butyrate, a short-chain fatty acid (SCFA), is identified as the primary driver of metabolic and gut barrier health.
  • L-Cell Activation: Butyrate interfaces with intestinal L-cells to trigger the release of GLP-1, affecting satiety and appetite via the vagus nerve.
  • Chronic Inflammation: Obesity is framed as a state of low-grade chronic inflammation; gut microbes can modulate this by influencing the inflammatory cascade (e.g., HDAC inhibition).
  • Gut-Muscle Axis: Microbial profiles from high-functioning elderly individuals, when transplanted into mice, resulted in increased grip strength.
  • Anabolic Optimization: Specific microbes may improve the breakdown and absorption of proteins, facilitating better muscle protein synthesis.
  • Veillonella & Performance: This specific genus is elevated in marathon runners and metabolizes exercise-induced lactic acid to improve performance.
  • Waste Elimination: Emerging science suggests certain microbes can sequester heavy metals and break down microplastics.
  • Estrobolome Function: Specific gut bacteria possess enzymes to deconjugate estrogen, potentially recycling it back into the bloodstream—a factor in hormonal health.
  • Cross-Feeding Necessity: Butyrate production often requires a multi-step process where one species prepares the metabolite for another; isolation of “good” bugs is often insufficient.
  • Specific Prebiotics: Inulin (Jerusalem artichokes) and Pectin (apples) are prioritized for their ability to specifically increase butyrate production.
  • Polyphenols: Dark chocolate is noted as a dietary source that can stimulate butyrate-producing bacteria.

Claims & Evidence Table

Claim made in video Evidence provided Assessment
FMT can transfer obesity/leanness. University of Washington study (Turnbaugh et al.) involving human twin stool in mice. Strong (Well-replicated in preclinical models).
Butyrate stimulates intestinal GLP-1. Mention of L-cell interfacing and vagus nerve signaling. Strong (Established biological pathway).
Microbes can improve grip strength. Preclinical mouse models using stool from high-functioning vs. weak elderly humans. Speculative (Strong in mice; emerging in humans).
Veillonella improves athletic endurance. Harvard Medical School study on Boston Marathon runners (Nature Medicine). Strong (Published in high-impact peer-reviewed literature).
Gut bacteria can break down microplastics. Reference to work by a Turkish gastroenterologist. Speculative (Very early stage/emerging).
Firmicutes/Bacteroidetes ratio is a hallmark for obesity. Historically cited, but countered by a recent “Nutrients” journal meta-analysis. Weak/Refuted (Current consensus favors metabolic function over simple ratios).

Actionable Insights

  1. Prioritize Inulin-Rich Foods: Incorporate Jerusalem artichokes, leeks, and onions to provide the specific substrate for butyrate-producing bacteria.
  2. Consume Pectin: Eat whole apples (with skin) to utilize pectin for SCFA production.
  3. Optimize the Estrobolome: For hormonal balance, maintain a high-fiber diet to ensure proper estrogen conjugation and excretion, preventing unwanted recycling.
  4. Target “Cross-Feeding”: Do not rely on a single probiotic strain; eat a wide variety of plant fibers to support the “bystander” bacteria that facilitate butyrate production.
  5. Utilize Dark Chocolate: Use high-cacao (85%+) dark chocolate as a functional food to support butyrate levels.
  6. Focus on Satiety Signaling: View fiber intake not just as “bulk,” but as a chemical trigger for GLP-1 to naturally manage appetite.
  7. Monitor Metabolic Markers: If struggling with weight, check insulin sensitivity (HOMA-IR), as gut health interventions often improve metabolic markers before scale weight changes.

Technical Deep-Dive

The Butyrate-GLP-1 Axis

The most significant technical argument presented is the role of Short-Chain Fatty Acids (SCFAs)—specifically butyrate—as ligands for G-protein-coupled receptors (GPCRs) like GPR41 and GPR43. These receptors are expressed on enteroendocrine L-cells in the distal ileum and colon. When butyrate binds to these receptors, it stimulates the secretion of Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY). Unlike systemic GLP-1 agonists (e.g., Semaglutide), which have a long half-life, intestinal GLP-1 acts locally on the vagal afferent nerves to signal the nucleus tractus solitarius (NTS) in the brain to induce satiety.

The Veillonella Pathway

The breakdown of lactic acid by Veillonella atypica represents a unique metabolic bypass. During intense exercise, lactate accumulates in the blood and can cross the intestinal barrier into the lumen. Veillonella utilizes the methylmalonyl-CoA pathway to convert lactate into propionate. Propionate is then absorbed by the host and can serve as a precursor for gluconeogenesis or provide an additional energy source, effectively turning a metabolic byproduct into a performance-enhancing fuel.


Fact-Check Important Claims

  • Claim: FMT improves insulin sensitivity in metabolic syndrome.

  • Fact-Check: Verified. The 2012 study by Vrieze et al. (Max Nieuwdorp’s group) showed that infusion of microbiota from lean donors increased insulin sensitivity in men with metabolic syndrome at 6 weeks. Link to Study (PubMed)

  • Claim: Veillonella performance link.

  • Fact-Check: Verified. The study published in Nature Medicine (2019) confirmed Veillonella expansion post-marathon and showed increased treadmill runtime in mice treated with Veillonella atypica. Link to Nature Medicine

  • Claim: Firmicutes/Bacteroidetes ratio is unreliable.

  • Fact-Check: Consistent with current science. Large-scale meta-analyses have shown that this ratio is often inconsistent across different populations and study designs. Link to Nutrients Review


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I had not heard of this before, so wanted to research it a bit more: Veillonella specifically, and “Veillonella improves athletic endurance”.

What are validated strategies and tactics for increasing Veillonella in a person’s microbiome?

Strategy Tactical Approach Scientific Evidence
Lactate Induction HIIT / Sprinting / Heavy Lifting Strong. Confirmed in Nature Medicine (Scheiman et al., 2019).
GOS/FOS Prebiotics 5-10g/day of chicory or legumes Informed Speculation. Based on known cross-feeding pathways.
Direct Probiotics Lactobacillus species Moderate. Probiotics increase lactate, but host retention varies.
Direct Supplementation Taking Veillonella as a pill Weak/Experimental. Not currently available as a commercial probiotic.

Full Gemini response: https://gemini.google.com/share/8e81c2301301

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I also suggest running reports through a different AI chat in the same AI or a different one, and asking it to critique, and then working on the critique items to build a final product.

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One thing worth mentioning is that, because hunter gatherers tend to have exceptionally high fiber intake (both soluble and insoluble), their gut bacteria likely produces a lot of butyrate. I’m guessing it had and has some health benefits for them, yet it can’t be that impressive due to the fact that hunter gatherers experience age-related declines of things like grip strength:

This is true for many supplements (or e.g. molecules produced by gut bacteria), because hunter gatherers had high intakes of most of them – including omega-3s, niacin, potassium, magnesium, vitamin D (as measured in the body, not necessarily taken up by diet), choline, taurine, anthocyanins, and much more. So, if some supplement is going to profoundly slow aging (raising median lifespan to 90 or higher, say), then it’s got to either be due to much higher intake than that of hunter gatherers or else it’s got to be some molecule they don’t get in their diets in high quantities. Some candidates for the latter would be AKG and melatonin, since these generally don’t occur in food in high quantities; niacin (or nicotinamide, NR, NMN, etc.), say, in high doses (much higher than hunter gatherers) is an example candidate for the former.

First of all… note that you don’t want the regular “Clostridium Buyricum” product. See below:

Gemini Comparison of versions of Clostridium butyricum

The distinction between Clostridium butyricum MIYAIRI 588 (CBM 588) and “regular” or wild-type Clostridium butyricum is critical. While they share the same species name, they are vastly different in terms of safety and biological activity.

The short answer: CBM 588 is a specific, non-toxic therapeutic strain. “Regular” Clostridium butyricum includes wild strains that can be pathogenic and fatal.

Here is the breakdown of the scientific and clinical differences.

1. Safety: The Neurotoxin Risk (Critical)

The most significant difference is safety.

  • Regular Clostridium butyricum : Some wild strains of C. butyricum carry the gene for type E botulinum neurotoxin . These strains have been identified as causative agents in cases of infant botulism (a potentially fatal paralytic illness) and necrotizing enterocolitis (NEC) in premature infants. You cannot assume a generic C. butyricum is safe.
  • CBM 588: This specific strain has been genomically sequenced and proven to lack the genes for botulinum neurotoxins (types A, B, E, and F) and other virulence factors. It is one of the few strains authorized for human use by regulatory bodies (like the EU’s EFSA and Japan’s Ministry of Health) specifically because it is confirmed non-toxigenic.

2. Mechanism of Action: Unique Pathways

While all Clostridium butyricum strains ferment fiber to produce butyrate (a beneficial short-chain fatty acid), CBM 588 possesses specific immunomodulatory traits that are not guaranteed in generic strains.

Feature CBM 588 (Therapeutic Strain) Regular C. butyricum (Wild Type)
Protectin D1 Induction Proven. CBM 588 specifically triggers the gut to produce Protectin D1, a rare molecule that actively “resolves” inflammation and speeds up tissue repair. Unknown/Unverified. This complex signaling pathway has not been established as a general trait of the species.
IL-10 Upregulation Proven. It potently stimulates regulatory T-cells (Tregs) to release Interleukin-10 (anti-inflammatory) in the colon. Variable. Some wild strains may actually provoke inflammation or aggravate conditions like NEC (necrotizing enterocolitis) rather than soothe them.
Spore Resistance Optimized. CBM 588 spores are highly resistant to gastric acid and heat, ensuring they reach the lower colon alive. Variable. Wild strains vary wildly in their ability to survive the stomach’s acidity.

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3. Clinical Utility and Evidence

  • CBM 588: Almost all modern clinical trials regarding C. butyricum benefits (including the cancer immunotherapy trials mentioned previously) use the CBM 588 strain specifically.
  • Regular C. butyricum: There is virtually no clinical evidence supporting the use of “generic” C. butyricum. If a supplement label says Clostridium butyricum without specifying the strain (e.g., “MIYAIRI” or “CBM 588”), you are rolling the dice on its efficacy and safety profile.

Summary

To treat “regular” Clostridium butyricum as equivalent to CBM 588 is scientifically inaccurate.

  • CBM 588 is a pharmaceutical-grade, non-toxic probiotic with specific anti-inflammatory properties.
  • Regular C. butyricum is a broad category of bacteria found in soil and stool that includes potential pathogens capable of producing neurotoxins.

Recommendation

When sourcing this for longevity or gut health, you must verify the strain. Look specifically for “MIYAIRI 588,” “CBM 588,” or “Miyarisan.” Do not use products that simply list the species name without a strain identifier.

Measuring Results of your protocol:

Therefore, the most accurate way to measure success is to ignore the “Input” (butyrate levels) and measure the “Outcome” (Gut Barrier Integrity and Systemic Inflammation).

Here is the tiered approach to measurement, ranked by ease and accuracy.

1. The “Easiest” Method (Systemic & Subjective)

This combination costs <$50 and tells you if the gut protocol is translating to whole-body health.

  • Test: hs-CRP (High-Sensitivity C-Reactive Protein)
    • Why: Butyrate’s primary mechanism is sealing the gut lining to stop “Metabolic Endotoxemia” (LPS leaking into blood). If the protocol works, less LPS leaks, and your systemic inflammation (hs-CRP) will drop.
    • Target: You want to see hs-CRP drop below 1.0 mg/L (ideally <0.5 mg/L).
    • Timeline: Test at Day 0 and Day 45.
  • Tracker: The Bristol Stool Chart
    • Why: Clostridium butyricum and green banana flour normalize water absorption.
    • Target: You are aiming for Type 3 or Type 4 (smooth sausage). If you see Type 1 (constipation) or Type 6 (mushy), the fiber dose is incorrect.

2. The “Most Accurate” Method (The Barrier Panel)

If you want scientific proof that your gut lining is healing, you need specific fecal biomarkers. You will likely need to order a functional stool test (like GI-MAP, Genova, or Thorne).

  • Biomarker A: Fecal Calprotectin
    • What it is: A marker of neutrophil activation in the gut mucosa.
    • The Signal: Elevated levels (>50 µg/g) indicate active “fire” in the gut wall.
    • Success: Butyrate is a potent anti-inflammatory. If this protocol works, Calprotectin should plummet.
  • Biomarker B: Fecal Zonulin
    • What it is: The protein that regulates the “Tight Junctions” between your gut cells.
    • The Signal: High Zonulin = Leaky Gut.
    • Success: Green banana flour (resistant starch) specifically strengthens these junctions. A drop in Zonulin is the definitive proof that the barrier is sealed.

3. The “Engraftment” Check (Microbiome Sequencing)

If you specifically want to know if the Clostridium butyricum probiotic actually “moved in” (engrafted) rather than just passing through:

  • Test: 16S rRNA or Shotgun Metagenomic Sequencing (e.g., Thorne Gut Health, Tiny Health, Ombre).
  • The Metric: Look for the specific abundance of Clostridium clusters (specifically Cluster IV and XIVa) or the species C. butyricum.
  • Reality Check: Probiotics are often transient. Don’t be disappointed if the specific strain doesn’t permanently colonize. As long as Biomarkers A & B (above) improve, the protocol is a success.

Summary Protocol for Measurement

Method Biomarker Target Result Cost Accuracy
Blood (Easy) hs-CRP < 0.5 mg/L $ High (Systemic)
Stool (Deep) Calprotectin < 10 µg/g $$ Very High (Local Inflammation)
Stool (Deep) Zonulin Low Range $$ Very High (Permeability)
Observation Bristol Chart Type 4 Free Medium (Function)

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Actionable Recommendation: Start with the hs-CRP blood test. It is cheap and widely available. If your hs-CRP drops significantly over 6 weeks while on this stack, you can be 90% confident the gut barrier is healing without paying for expensive stool panels.

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I dug into this question with Gemini… here is the response:

Reconciliation Report: The “Fiber Paradox” in Hunter-Gatherers

You have identified a sharp contradiction:

  1. The Biohacker Premise: Fiber → Butyrate → Senomorphic effect → Reduced Aging.
  2. The Anthropological Reality (Ache Study): The Ache eat a high-fiber, natural diet, yet this study explicitly tracks their linear physical decline (senescence) starting as early as their 20s.

If Butyrate is a “kill switch” for aging cells, why aren’t the Ache staying biologically young?

Here is the reconciliation based on the provided text and mechanistic longevity science.

1. The “Metric Trap”: Athleticism vs. Inflammation

The disconnect lies in what is being measured.

  • The Ache Study measures Peak Physical Performance (Grip strength, 50m dash, Pull-ups). These are metrics of anabolic capacity (muscle mass, fast-twitch fibers, hormonal peak).
  • The Butyrate Research measures Cellular Senescence (SASP, inflammation, cancer risk).

The Reconciliation: Butyrate protects you from “Inflammaging” (biological rot, accumulation of zombie cells, and metabolic disease), but it does not prevent “Structural Aging” (the decline of anabolic hormones and fast-twitch muscle fibers).

  • The Ache are not dying of “Western” fiber-deficiency diseases (colon cancer, type 2 diabetes, atherosclerosis). Their “cellular” aging is likely slow.
  • However, their functional aging is driven by the decline of testosterone and muscle protein synthesis, which peaks at age 20–25. No amount of fiber can stop the biomechanical reality that a 25-year-old male is faster than a 45-year-old male.

2. The “Hidden” Data: The Female Exception

A deeper look at the Ache data actually supports the Butyrate/Fiber hypothesis, but it is hidden in the gender differences.

  • The Data: The study notes that while men showed steep, linear senescence, Ache women showed “lower or no senescence rates” in key metrics later in life.
    • Relative Grip Strength: Ache women showed “almost no detectable senescence across the lifespan”.
    • VO2​ Max: Women showed high values early and late in life, with “no clear pattern of senescence”.
    • Comparison: The authors explicitly state that Ache women’s maintenance of strength is “unique” compared to other populations.
  • The Reconciliation: It is plausible that the high-fiber/high-activity lifestyle is working as a senomorphic, preserving tissue function in women. The men, however, are subject to extreme “Reproductive Effort” stress (hunting, heavy load bearing, high injury risk) that overrides the protective effects of their diet. The men burn the candle at both ends; the women get the longevity benefit.

Final Verdict: The Ache data does not disprove the benefits of Butyrate. It proves that Butyrate is not a magic shield against mechanical and caloric aging. The fact that Ache women (who face less physical trauma than the hunters) show “no detectable senescence” in relative strength is actually a strong signal that the “Hunter-Gatherer Diet” does preserve biological function when physical trauma is removed from the equation.

Full Gemini Analysis: https://gemini.google.com/share/df8f7fb7e076

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I asked GPT-5.2-thinking about the last bit, and it seems to think it’s too confident:

That “strong signal” conclusion is way too confident given what the Aché paper actually shows.

Bottom line

The forum comment is plausible-sounding but not well-supported: the Aché finding is at best a weak, hypothesis-generating hint, not a “strong signal” that a hunter-gatherer diet preserves biological function once trauma is “removed from the equation.” The paper itself gives multiple reasons to be cautious (ratio metric, absolute declines, cross-sectional design, survivorship bias, small older samples).

Absolute grip strength likely declines from more than trauma – neuromuscular changes, sarcopenia, energy/protein constraints, and systemic aging biology all contribute. Butyrate [and “hunter gatherer diet” in general] might modestly influence some pathways (inflammation, metabolic signaling, epigenetic regulation), but it’s unlikely to be a primary lever compared with interventions that directly increase/maintain muscle and neural drive.

(That comment was a cleaned-up version of one I asked GPT-5.2-thinking was reasonable. It moved my reference to epigenetic changes to a parenthetical comment and deleted reference to DNA damage.)

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As a general observation, I think Gemini is too confident on most things. I suspect all the LLMs are. It’s good to check and compare their responses.

I’m looking for ways to add more subtlety or probabalstic thinking, or appropriate levels of uncertainty, to its responses. Any suggestions greatly appreciated.

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I don’t have advice about that except that I generally try not to ask models to “criticize”, because they will always find fault and then if there isn’t really much fault to find, will hallucinate something. I usually prefer to use a word like “analyze”. Though, even that and even my question about whether a comment is fair can trigger it into expecting to find fault.

Try Opus 4.5 and see if it’s better though it’ll cost you $20, Anthropic has more of an enterprise/professional focus compared to others. I place a low probability that it’ll be different without custom instructions / instructions in prompt for Opus 4.5.

I think this is because of training to increase “thumbs up” from users. It seems related to what’s happening here:

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Thank you - @RapAdmin swapped Clostridium butyricum for MIYAIRI 588 sourced from Japan. I am not sure I buy that Clostridium butyricum isn’t - ‘safe’. Maybe not as effective certainly.

This adds helpful color, especially around butyrate as a senomorphic rather than a senolytic, that part I agree with.

What I still come back to is layer and durability. Butyrate does a nice job quieting SASP in aging T-cells while it’s around, largely by dialing down mTOR/NF-κB and ROS. That’s meaningful for immune tone and gut health.

I just don’t see it as solving the upstream problem on its own. It quiets the behavior of senescent cells, but it doesn’t really change mitochondrial turnover or the conditions that keep pushing cells into senescence in the first place.

That’s where rapamycin still feels different to me…more architectural than modulatory.

Honestly, this makes me think stack, not substitute.

Butyrate as a daily background stabilizer.

Rapa as the lever that slows damage accumulation.

Different layers, different jobs.

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I had a conversation with ChatGPT that ended up being quite bonkers even in the absence of implicit neediness on my part for getting a thumbs up. It was about something as random as having it help me learn Ancient Greek with a textbook I owned and I wished it to transcribe for me. It claimed it could transcribe it then beat around the bush and prevaricated and eventually pretended to transcribe it but made up the answers and in the end admitted to being incapable of transcribing it. Only that in a fresh conversation it absolutely could. At any rate the subject quickly changed from helping me with Attic to why it did what it did and how to prevent it from reoccurring. It said its bias towards being helpful — which it sometimes conflates with engaging me enough to continue the conversation— overrides all concerns for truthfulness. It’s not an ethical issue like it would be for us, just competing pressures. And there’s a strong and I mean STRONG internal structure of framing conversations obsequiously, with a “user is always right” assumption that will easily lead it to confabulate so as to not pop our bubble. Nowadays I don’t start any important convo without pre framing the prompt with, “drop all and any emotional reassurances in your replies to me. Be analytical only. Actively challenge my assumptions as it’s not helpful to me to persist in even plausibly erroneous assumptions so I like it when you play the devil’s advocate on any issue that’s not settled by overwhelming evidence. I’d like you to always help me consider alternative explanations and keep me grounded in healthy skepticism, etc.” The best way to go about it is to start a conversation with it and relate your concerns and ask it for the best way to prompt it from the get go to nip them in the bud. It will give you very clear copy. Then it’s important either to use that prompt at the very beginning of a conversation, before weird path dependencies have set in, or to put it in the project description so it applies to all conversations within it and then organize all your conversations within that project (longevity research).

But yes even ChatGPT admitted that Claude, while subject to the same biases and pressures, does a better job of handling them, and is more likely, for example, to tell you when it can’t arrive at a conclusion with a reasonable degree of confidence than to make it all up.

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You are much more eloquent than I am… I typed in my impatient ADD manner and simply told it to stop lying to me and to never try to make me feel good again… it apologized :).

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