Can certain fungi or bacteria in your gut influence your cellular ageing?
There are serious indications that gut bacteria can drive cellular ageing, but this has not yet been proven in humans. Concrete steps via probiotics or prebiotics still lack clinical support, so it is too early to act on this now.
Certain gut bacteria produce a substance called phenylacetylglutamine (abbreviated PAGln). Older people produce more of this substance than younger people. In cell and mouse studies, PAGln was found to age cells by damaging the cell's energy factories (mitochondria) and causing DNA damage. The cell then becomes, in effect, locked in a damaged state, also known as cellular ageing or senescence. This mechanism is well described biologically, but it has not yet been demonstrated in living humans.
More broadly, the gut microbiome changes in composition with age: there are fewer species of bacteria, and relatively more harmful species grow. Multiple review studies link this to more chronic low-grade inflammation and more senescent cells in the body. The two phenomena are strongly associated, but whether the bacteria cause cellular ageing or vice versa has not yet been definitively established. It likely works in both directions: senescent cells secrete inflammatory substances that in turn further disrupt the gut environment, which reinforces the process once more.
It is tempting to think that you can slow this process through probiotics or prebiotics, but clinical evidence in humans is largely lacking. Review studies mention this approach as a conceivable direction; for now, that is as far as it goes. In mouse studies, it did prove possible to reduce PAGln-driven cellular senescence, via two strategies: blocking the receiving antenna that PAGln acts on (the adrenergic receptor) or administering senolytics, agents that clear out aged cells. Clinical trials in humans do not yet exist.
A large overview study on anti-ageing interventions acknowledges the gut microbiome as a potential target, but the agents with the strongest clinical evidence are currently others: drugs such as rapamycin and metformin take the top spots. The microbiome does appear on that map, but has not yet scored at the top. All in all, there are solid mechanistic indications that your gut bacteria can influence your cellular ageing, but the step from rodent study to proven effect in humans has not yet been made.
Claims based on cell and mouse studies (PMID 39794469), multiple review studies on microbiome and senescence (PMID 39148278, 34960102), a broad anti-ageing review (PMID 32467649), and a study on post-menopause and the gut microbiome (PMID 39585466). No large randomised trials in humans are available for the microbiome-senescence link.