向小鼠鼻腔输送鞭毛蛋白（FP）可延长小鼠的寿命和健康寿命。
它还导致“脱发和晶状体混浊减少、骨矿物质密度增加、干细胞活性提高、胸腺复旧延迟、认知能力提高以及肺纤维化的预防。
类似雷帕霉素的寿命延长
科学家们使用了 21 个月大的小鼠，这大约是这些动物发生与年龄相关的免疫衰老的时间。对小鼠进行鼻内 FP 治疗八个周期。这以性别依赖性的方式延长了寿命，雌性小鼠受益更多。考虑到治疗开始的时间有多晚，结果是显着的。
关于这一新发展的文章：
这些方面之一是病原体识别受体（PRR）活性降低。顾名思义，PRR 的作用是识别病原体并发起免疫反应。虽然 PRR 是先天免疫系统的一部分，但它们的功能障碍也会影响适应性免疫，例如向 T 细胞呈递抗原的效率较低。这可能是老年人对新冠疫苗反应不那么明显的原因之一。人们已经探索了各种用于疫苗的 PRR 靶向佐剂（补充药物）。
Toll 样受体 (TLR) 可能是最重要的 PRR，因为它们识别病原体相关分子模式 (PAMP)。 TLR 的活性因衰老而减弱，导致疫苗反应减弱[3]。在《自然通讯》上发表的这项新研究中，一组科学家试图刺激这些受体的一个子集（称为 TLR5），以减轻小鼠与年龄相关的免疫衰老。
完整研究论文：（开放获取）：粘膜 TLR5 激活控制健康寿命和寿命 |自然通讯
乳酸菌（例如酸奶中的乳酸菌）可以刺激 TLR5 受体
酸奶和酸奶发酵过程中产生的液体可能就是这样。请参阅下文和研究链接。
https://www.sciencedirect.com/science/article/pii/S1756464620300074
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The L. rhamnosus is a strain that might be worth checking out
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Bicep
#3
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So, can we do a group buy and share the starter and grow it ourselves? What do you think?
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Bicep
#5
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.
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jnorm
#7
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).
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Lost
#8
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!
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EnrQay
#9
I’d like to. I’m experienced in making yogurts from various strains, so no problem there. But how to get it from ADM?
medaura
#10
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.
J0hn
#11
I agree, you will also need a bench top centrifuge possibly refrigerated, pH meter or other means of measuring pH and a freeze drier.
Jay
#12
jnorm, Yes, that is what I read also. The ADM product did not refer to the cell-free supernatant.
medaura
#13
Eventually this molecule might become something a lab can order online but I bet it’s a few years away at least.
Bicep
#15
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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Bicep
#17
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…
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Bicep
#19
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.
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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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