ageing, animals, cancer, microbes

Aging and the Gut Microbiome

The more we learn about them, the clearer it’s becoming that the microbiomes that surround us – and live inside of us – serve vital functions for us. (Microbiomes are collections of microbes, such as bacteria and yeast, which live together in a certain area.) Just last week, we looked at the microbes living in Beijing’s dense smog, which include several pathogenic and allergenic species. And a couple of months ago we explored many recent discoveries in the field of the gut microbiome, including how obese individuals have a less diverse microbiome than “lean” individuals. A relevant recent study explored how the gut microbiome is also related to aging.

Drosophila melanogaster
Drosophila, a fruitfly used as a model to investigate aging and the gut. (Image credit: Botaurus)

The study, which was done in the fruitfly Drosophila, aimed to explore how the gut changes as animals age in general, using the fruitfly as a model. As one author explained, we already knew that “age-related changes in the gut … include increased oxidative stress, inflammation, impaired efficiency of the immune response, and the over-proliferation of stem cells.” But what’s responsible for these observed changes? Which changes (if any of these) cause the others to take place? And what does the gut microbiome have to do with it? In their study, the authors helped answer these questions in Drosophila.

The number of bacteria living in the fruitflies’ guts increases significantly with age, and this is thought to cause the inflammation which, in turn, can cause a pre-cancerous state associated with aging. The researchers showed that the misregulation of an early player in a complex signaling pathway is, at least, partly to blame. Specifically, as the fruitflies age, a gene (called Foxo, a transcription factor) becomes activated more than it should. This player normally suppresses a protein (peptideglycan recognition protein SC2, or PGRP-SC2) that’s responsible for regulating how the fruitfly’s immune system responds to bacteria. So, because Foxo becomes activated more, it prevents the immune system from keeping the number of gut microbes in check, and the microbe numbers increase. This, in turn, leads to inflammation, rapid production of stem cells, and potentially pre-cancerous conditions in the gut.

Interestingly, when the researchers increased the amount of PGRP-SC2 protein in the gut, the number of gut microbes and stem cells decreased back to normal levels. Furthermore, adding this protein increased the lifespan of the fruitflies. It’s definitely a promising avenue to explore for potentially improving the lifespan of humans.

So while there are rarely ever quick and easy answers for solving a complex biological puzzle such as aging, with the help of key model organisms like Drosophila we can still put the pieces together one at a time, and continue to get one step closer to making out the bigger picture.

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