"Cell": Life expectancy is extended by up to 40%! Chinese scientists open the door between gut microbes and longevity
Release date: 2017-06-20
Today, a study revealing gut microbes and aging from the genetic level is published in the journal Cell!
Professor Wang Meng from the Baylor College of Medicine led a team to model the C. elegans strain, and screened nearly 4,000 E. coli strains with different mutations in the body, and found dozens of them to prolong life and delay tumor development and β. - The gene that is accumulated by amyloid! And also found a compound that can be "continued" - colanic acid (CA) [1]!
Professor Wang Meng
In recent years, more and more studies have shown that changes in intestinal microbes are related to the aging process of the host. However, most of the research is limited to group research and metagenomic analysis, and the exploration of the gene function and molecular mechanism of single microorganisms is still lacking.
In this context, the significance of this research is undoubtedly very significant. It links intestinal microbial-gene-aging-age-related diseases together, and identifies specific compounds that work, providing new ideas for the practical application of the research, which can be said to "open intestinal microbes." Resist the door to aging and prolong life."
Not only that, but when they discovered CA, they also revealed that CA is delaying aging through mitochondria. Mitochondria, as an "energy factory" in cells, have had some discoveries about the relationship between aging and aging. But this study is the first to prove that intestinal microbes can actually "communicate" with mitochondria through metabolites. It seems that the intestinal microbes can not only communicate with the distal organs, but also the organelles, which can be regarded as "pervasive"!
Mitochondria
Why is E. coli used in research? Because Caenorhabditis elegans feeds on bacteria such as Escherichia coli, in laboratory culture, E. coli colonies are usually grown on the medium, and the nematode larvae live in it. In this way, E. coli colonizes the larvae of the nematode larvae, and as the nematode grows up, it forms the intestinal flora of nematodes [2].
In this study, in order to comprehensively and deeply understand the impact of E. coli gene layer on lifespan, the researchers established an E. coli single gene knockout library, which includes a total of 3,398 single-gene mutant strains. They separately fed each strain to the nematodes and observed their lifespan. After testing, the researchers found that 29 mutants can extend the lifespan of the nematodes by more than 10%, the most significant of which is the hns mutation, the nematode Life expectancy is extended by as much as 40%!
29 mutations that extend the lifespan of nematodes (the first is the hns mutation)
In addition, the researchers attempted to introduce mutations into wild-type E. coli (MG1655) and found that 23 of them were still effective. Moreover, even across the larval stage, from the adult to the feeding of mutant bacteria, there are still 21 kinds of bacteria to maintain their ability to extend life.
This led the researchers to an idea that the regulation of intestinal life by gut microbes is unquestionable, and that these regulation are independent of the developmental stages of specific microbial strains and hosts. This means that all microorganisms with these mutations, regardless of the stage of development at which they occur, can contribute to the extension of life.
Of course, if researchers want to “manufacture†probiotics through genetic engineering to help us prolong life, it seems to be feasible on the basis of this research! "The secret of Changshou Village" is no longer a secret. Imagine if we could drink a probiotic yogurt for a long time in the future. Is it not a good thing?
Of course, living longer is not the ultimate goal, and healthy living is longer. If the disease is ridden, it doesn't make much sense to live long, so the researchers also verified whether the mutant can cope with the disease caused by aging.
The researchers asked the nematode to express human β-amyloid and germ cell hyperproliferative tumors. They found 16 mutations that increased the survival rate of tumor nematodes, 14 mutations that prolonged the lifespan of "dementia", and 12 delays. Dementia" nematodes lose mutations in their ability to exercise. A total of 13 coincident mutations have appeared, which have a “protective effect†on both nematodes. This explains in a sense that these 13 mutations can help improve the overall quality of life of the host.
Coincidence of two groups of nematode mutants
So if you open your brain, maybe the probiotic yogurt we envisioned before can also help some elderly people who are sick?
In many years of research, scientists have revealed several molecular or signaling pathways involved in longevity, including insulin/insulin-like growth factor 1 (IGF-1) and rapamycin target protein (TOR) signals. Pathway and caloric restriction (CR). In this study, the researchers also found that most of the mutants extended the lifespan of the nematodes through the IGF-1 and TOR signaling pathways, and only four mutants were restricted by calories.
However, these results do not include two mutants, one of which is the hns mutation that maximizes the lifespan of the nematode, and the other is the lon mutation, which extends the lifespan of the nematode by 25%. These two mutations do not work through the above three known ways, which makes the researchers very curious. If you can find this "mysterious way", it means that in the long-lived "customs clearance", we Can I get a valid prompt?
Sporting nematode
When the researchers were struggling, they suddenly discovered that there was an "unusual" connection between the two genes - they were involved in the synthesis of a metabolite! This metabolite is colanic acid (CA). So the researchers boldly guessed, would they use the CA molecule to extend the lifespan of nematodes?
With a bold guess, you need to be careful to verify that they first tested the amount of CA in the medium and found it to be very high, and the hns and lon media were higher than others. In addition to prolonging lifespan, these mutants containing a large amount of CA also attenuated the mitochondrial breakdown of the aging-related muscle mitochondria, and the mitochondrial breakdown and functional decline of the body wall muscle is a significant sign of somatic aging [3].
To prove the efficacy of CA, the researchers fed CA directly to the nematode and found that the lifespan of the nematode was extended by 20%! For nematodes with beta-amyloid and germ cell tumors, CA intake also improves their exercise capacity and survival time. In addition, fruit flies that ingested CA in the experiment also showed an increase in lifespan.
The lifespan of nematodes increased by 20% after feeding CA (black for control, orange for CA)
So how does CA extend life? This is related to the mitochondria we just mentioned. After ingestion of CA, it regulates mitochondrial division and promotes mitochondrial unfolded protein responses. Mitochondria is a very important organelle in all eukaryotic cells. It is the "energy factory" of cells, which supplies cells and participates in the regulation of cell growth.
This finding seems to tell us that gut microbes use their own metabolites to “fuel†the mitochondria, maintaining the “normal functioning†of the energy plant, so that the mitochondria can tirelessly provide energy for cell activities and keep the cells “youngâ€. .
Decreased mitochondrial function or barrier is a sign and driver of aging, and protein unfolding is one of the causes of mitochondrial dysfunction. After being absorbed by intestinal cells as a metabolite, CA associates with the mitochondria in the cell, helps unfolded protein response under stress conditions, undergoes correct folding, restores mitochondrial signaling, and maintains mitochondrial function and protein. Steady state, "continuation" for nematodes. Not only that, but this mechanism can also occur in mammalian cells, and with the previous fruit fly, the researchers believe that this mechanism is evolutionarily conservative.
If you continue to dig deeper, CA can help the unfolded protein response through the transcription factor ATFS-1, such as the mutation of the atfs-1 gene, so that ATFS-1 loses its function, then CA can extend the life expectancy.
Schematic diagram of the regulation of CA and mutant bacteria on the lifespan of nematodes
For this, Professor Wang Meng said: "The mitochondria seem to have evolved from bacteria that entered the cell millions of years ago. Our research shows that, millions of years later, bacteria can still occur with mitochondria in our cells. 'Communication', we believe that this communication is very important, and here we also provide evidence for microbial and mitochondrial communication for the first time."[4]
In today's "Cell" magazine, researchers from the National University of Singapore have also written a review article [5]. They pointed out that two of the results of this series of studies are very noteworthy. One is that CA helps unfolded protein responses under stress conditions, suggesting that CA may be used as a means of counteracting intestinal microbial stress in the future. It may be good for many stress-producing diseases.
The other is that the direct complement of molecules represented by CA is also an inspiration for humans. This is back to the probiotic yogurt we mentioned earlier. It seems that it is also a good choice to add CA directly without adding probiotics.
All in all, although this study is only carried out in the worm, it is essential to help researchers better understand the relationship between gut microbes and aging. Moreover, key molecular compounds have been identified, and there must be no application areas. Small inspiration, let us see the hope of "longevity".
Reference material
[1] http://(17)30627-X
[2] Clark, LC, and Hodgkin, J. (2014). Commensals, probiotics and pathogens in the Caenorhabditis elegans model. Cell. Microbiol. 16, 27–38.
[3] Regmi, SG, Rolland, SG, and Conradt, B. (2014). Age-dependent changes in mitochondrial morphology and volume are not predictors of lifespan. Aging (Albany NY) 6, 118-130.
[4] https://
[5] http://(17)30641-4
Source: Singularity Network (micro signal: geekheal_com)
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