Mucosal TLR5 activation controls healthspan and longevity (Nature)

Nasal delivery of a flagellin protein (FP) in mice increased their lifespan and healthspan.

It also led to "diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis.

Rapamycin-like lifespan extension

The scientists used 21-month-old mice, which is roughly when age-related immunosenescence occurs in these animals. The mice were treated with FP intranasally for eight cycles. This increased lifespan in a sex-dependent manner, with female mice benefiting more. The results were remarkable, given how late in life the treatment began.

An article on this new development:

One of those aspects is reduced activity of pathogen recognition receptors (PRR). As their name suggests, PRRs’ role is to recognize pathogens and mount an immune response. While PRRs are part of the innate immune system, their dysfunction also affects adaptive immunity, such as in less efficient presentation of antigens to T cells. This might be one of the reasons why older adults show less pronounced response to COVID vaccines. Various PRR-targeting adjuvants (complementing drugs) for vaccines have been explored.

Toll-like receptors (TLRs) are probably the most important PRRs, as they recognize pathogen-associated molecular patterns (PAMPs). TLRs’ activity is blunted by aging, causing diminished vaccine response [3]. In this new study published in Nature Communications, a group of scientists attempted to stimulate a subset of those receptors called TLR5 to alleviate age-related immunosenescence in mice.

The Full Research Paper: (Open Access): Mucosal TLR5 activation controls healthspan and longevity | Nature Communications

Lactic acid bacteria, such as in yogurt, can stimulate TLR5 receptors

yoghurt and the liquids produced during yoghurt fermentation might be the way. See below and research link.


The L. rhamnosus is a strain that might be worth checking out


And here’s where you get it:

Increases IL-10 by 57%

db3b07342fd2484b8826e732b5f154a3.aspx.pdf (1008.0 KB)

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So, can we do a group buy and share the starter and grow it ourselves? What do you think?


Really hard to find where to buy this stuff. If they’re making bulk you would think somebody would be buying it and putting it into pills or bags, right? We can’t be the first ones to see this:

Somebody can give this a try and report back tomorrow. Past my bed time.



Related Research:

A skin company has started using the product:

The patent:

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I’d think you’d want the cell-free supernatant, especially if the bacterium itself induces TLR2 and TLR4. TLR4 is pro-inflammatory and is linked to allodynia and hyperalgesia. Definitely something I’d be careful playing with.

Theoretically you could use something like (+)-naloxone, which lacks opioid affinity while acting as a TLR4 antagonist, but this seems unnecessarily complicated and probably quite difficult to source.

Procedure for isolating cell-free supernatant.

The CFS was obtained by centrifugation at 12 000 g for 10 min, neutralised with 1 M–NaOH to a pH of 7·0, concentrated 10-fold by lyophilisation and then sterilised by filtering through a 0·22 μm filter (Minisart hydrophilic syringe filter; Sartorius Stedim Biotech GmbH). The supernatant was added at a concentration of 7 % (v/v).


I’m a bit worried that the hybrid protein gets results but the flagellin component, despite activating TLR5, did not.

One might like to compare with, say, Reporting on a Study of One with Flagellin Immunization to Adjust the Gut Microbiome – Fight Aging!


I’d like to. I’m experienced in making yogurts from various strains, so no problem there. But how to get it from ADM?

I read the whole paper. No way it can be DIY-ed at home unfortunately. One would need a couple biochemists in a lab. And scouring pubmed for simpler stuff to selectively activate / up-regulate TLR5 yielded nothing but smoke and mirrors.

I agree, you will also need a bench top centrifuge possibly refrigerated, pH meter or other means of measuring pH and a freeze drier.

jnorm, Yes, that is what I read also. The ADM product did not refer to the cell-free supernatant.

Eventually this molecule might become something a lab can order online but I bet it’s a few years away at least.

MSP-102 is the compound.

In addition to MSP-306, which is being developed for NASH, Medispan is also developing MSP-102 as an anti-aging drug for osteoporosis, sarcopenia, cataracts, and hair loss. MSP-102, which is being developed as an intranasal drug candidate for convenient dosing in elderly patients, has already shown multifaceted functional improvements in various animal models and a lifespan extension effect of 8% in male mice and 13% in female mice.


Specifically, L. rhamnosus CNCM I-4036
compared to baseline:
• Increased levels of anti-inflammatory molecules
IL-4 +41% IL-10 +57%
• Improved anti-inflammatory / pro-inflammatory
molecules ratio
IL-10/IL-12 +66%
• Decreased levels of the pro-inflammatory index
TNF-α/IL-10 -25%

@John_Hemming can you explain why they are calling IL-10 anti-inflammatory? I though it was bad and associated with SASP? This quote is from the ADM flyer above.

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Il-10 inhibits nf kappa b and is therefore anti inflammatory but it has the effect of cutting citrate from the mitochondria and causes senescence.

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This stuff is so confusing. So you probably would not want to take the probiotic and activate TLR5? It did make mice live longer. So confusing.

The crazy thing is that they get the probiotic from the feces of babies and in babies senescent cells probably do something good. They might do something good in us too for all we know.

Luckily we don’t have to decide now whether to take it because I sent at least 3 emails to ADM trying to figure out where we could buy this fancy product and nobody even answered.

Thanks for the reply

It’s a commercial product so I doubt they sell less than 50 kilo bags. Their customers are companies that will be buying thousands of kilos for manufacturing of new products…


I did finally get a reply from the account manager for probiotics and enzymes. I know that replying to me is a poor use of her time, but her email was on the flyer. She sent me 4 more pamphlets of probiotics they sell and said this is all we sell, if you need anything else let me know. So I sent her the pamphlet for ( L. rhamnosus CNCM I-4036) and said I want this one. Lol, we’ll see if I get anything back.

Since she was kind enough to reply, I’ll try to post the 4 pamphlets she sent me:

Munispore.pdf (605.3 KB)

That one is supposed to improve immunity starting with the gut.

BPL1 Probiotic.pdf (2.3 MB)

That one is supposed to make you skinny

DE111.pdf (1.8 MB)
That one is supposed to make SCFA, improve immunity, crowd out pathogens and take up residence.

ES1 Probiotic.pdf (728.7 KB)

This one is mostly for inflammation.


Actually pretty easy to buy l rhamnosus in compound pharmacies in brazil. I imagine it is the same in the usa.

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