Longevity Briefs: Is Our Own Gut Eating Us?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The mucosal membrane in the intestines forms a barrier between the contents of our gut and the rest of the body. This barrier is increasingly disrupted during ageing, and it has been suggested that this might contribute to further ageing and age-related diseases through various mechanisms. For example, it may contribute to the disruption of the immune system and the gut microbiome. In this study, researchers propose a new and unexplored mechanism: autodigestion.

We have evolved to be able to digest other organisms, which means that the enzymes produced by our digestive tracts have the ability to break down most of the molecules that we ourselves are made of. The only reason they don’t is that they stay within the gut. But what if some of them can get past the weakened mucosal membrane in old age?

The discovery:

The researchers used antibody staining techniques to detect the presence of trypsin, a pancreatic enzyme that breaks down proteins. They found that young (4 month old) rats had very low levels of trypsin in multiple organs including the liver, lung, heart, kidney, brain and skin. They also detected trypsin within the walls of the small intestine (whereas it should remain restricted to the intestinal lumen – the cavity inside the intestines). However, 24 month-old rats (approximating roughly to a human in their 50s) had significantly higher levels of trypsin in these organs. Similar results were found for other pancreatic enzymes.

The researchers then tried feeding the rats a trypsin inhibitor, and found that this significantly reduced the accumulation of trypsin in these organs, though only in the brain was trypsin reduced to levels comparable to those in younger animals. More importantly, the researchers found that this treatment appeared to be associated with some health benefit. Treated rats had less age-related degradation of collagen, a protein that holds cells together and gives tissues structural rigidity. They also had reduced blood sugar, which appeared to be because of reduced damage to receptors for the blood sugar lowering hormone insulin. The treatment even appeared to strengthen the mucosal barrier (since this too is attacked by trypsin), which in turn reduced the escape of other enzymes from the gut.

The implications:

This study suggests that as the intestinal barrier weakens with age, some digestive enzymes could escape and reach other organs where they degrade important proteins. They even appeared to reach the brain, meaning they crossed not only the intestinal barrier but also the blood-brain barrier. This could be a meaningful contributor to the ageing process, but needs to be confirmed in human studies. Inhibiting these rogue digestive enzymes in humans would in theory be quite easy, but steps would need to be taken to ensure that digestive processes were not negatively impacted.

In the meantime, there are some relatively safe practices we could adopt that might reduce the potential for digestive enzymes to escape the gut. The first is to adopt diets that include fasting, time restricted feeding or really any diet that reduces or eliminates food intake over a prolonged period. This may give mucosal barriers more time to regenerate after a meal, and may even partly explain why these practices seem to delay ageing, at least in animals. The second is to avoid high fat diets and alcohol, as both of these can degrade the mucosal barriers. Remember that significant dietary changes should be approached with caution.