Inside every cell there are waste-recycling stations: lysosomes. To digest the trash, they need an acidic environment, and the acid is pumped in by a molecular pump called V-ATPase. With age this pump works more and more weakly, and lysosomes stop keeping up. But the bacteria living in the gut have their own building material, peptidoglycan, and as it turns out, it can serve as a key that restarts the pump.
Scientists noticed that aging worms accumulate undigested bacteria in the gut, while old mice show falling levels of lysozyme, the enzyme that cuts the bacterial cell wall. This means that with age less peptidoglycan enters the body. So the researchers added purified peptidoglycan to the food of worms and mice. The result was striking: the worms lived on average 10% longer, and the mice 9.7-11% longer depending on sex, with maximum lifespan in males rising by 21%. The old animals improved their mobility, grip strength, and coat condition.
It turned out that peptidoglycan gets inside cells, finds lysosomes, and binds directly to the pump, enhancing its work. The lysosomes become more acidic, and the shredder enzymes, cathepsins, start working more actively. This was confirmed by direct measurements: in cells treated with peptidoglycan, lysosomes glowed a more acidic color. And if the pump was blocked with the inhibitor bafilomycin A1, the entire effect disappeared. In worms with a mutation in one of the pump subunits, peptidoglycan did not extend lifespan.
This work shows for the first time that bacteria are not only a source of metabolites or immune stimuli, but also suppliers of molecules that support intracellular infrastructure. Previously no natural molecule was known to directly activate V-ATPase and restore lysosomal acidification. Now such a key has been found, and it lies in a lock we carry in every cell. What remains is to find out which particular peptidoglycan fragment is the most active, and to test whether this works in humans. If it does, the bacterial cell wall could become the basis for supplements that slow aging and support lysosomal function in age-related diseases.
Peptidoglycan is the very molecule that makes up the bacterial cell wall, and it is what our innate immune receptors recognize to trigger inflammation. Now it turns out that the same molecule can act as a molecular tonic for lysosomes.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.