The microbiome – the key to longevity?
Research into to how ageing can be reduced is all the rage these days. Among the most prominent initiatives specifically addressing slowing and even reversing of ageing are the Google and Abbvie supported company >>> Calico and the foundation >>> Sens, in addition to a range of research groups at academic institutions around the globe. The billions of dollars (>>> Bloomberg) that are being invested in this sector shows that the idea of finding “the fountain of youth” is not part of science fiction anymore.
What about the microbiome in ageing?
If you are not new to this site, or to the world of the microbiome, this will be of no surprise to you: Mechanisms specific to ageing also can be influenced by the microbiome, and most likely this includes diet-microbiota-host interactions. (Mehr dazu: Fountain of Youth - it lies within your gut)
As an example a group of Spanish researchers write in a recent review article: “Emerging evidence has suggested that exogenous polyamines (either orally administrated or synthetized by the gut microbiota) are able to induce longevity in mice, and that spermidine supplementation exerts cardioprotective effects in animal models.”
So, what are polyamines and what can influence the amount and types of polyamines that are produced by the microbiota?
Polyamines are substances essential for key cellular functions, such as stabilizing DNA, protection against oxidative stress and programmed cell death. Examples of these substances are spermidine, spermine, cadaverine and putrescine (the two latter are diamines to be more precise). The substances are endogenously (means by ourselves) produced, but of late, the exogenous (non-self-produced) contribution of polyamines to the metabolism have been found to play a role too. Exogenous sources are: Preformed polyamines in the diet, and polyamines formed by the gut microbiota.
Polyamines in our food
In the first >>> study of its kind - a prospective cohort study (study with a group of healthy individuals) where dietary intake was assessed - spermidine was found to be the strongest predictor of reduction in mortality among the 146 nutrients studied. The difference between the top and bottom third in spermidine intake was comparable to that associated with a 5.7 years younger age in the on average 65 years old participants, according to the authors. It is notable that the best sources of spermidine in the diet include several items not generally recognized as the most healthy ones, thus reducing the potential influence of healthy lifestyle confounding on the found associations. These data in humans build on the longevity effects seen in mice, and indicate that amounts of spermidine in normal foods can be sufficient to make a difference.
But what about the role of individual differences in the microbiota? Are there big differences in how much polyamines are produced comparing microbiotas from different individuals? In the review mentioned above, the authors write: "... experiments in rats using different dietary interventions demonstrated that the oral administration of fermentable fibers and fructans stimulates certain intestinal microbial species (i.e., bacteroides and fusobacteria) to synthesize large amounts of polyamines in the large intestine."
However, there is too little data available to claim that the presence or lack of certain strains of bacteria in the human colon will affect polyamine levels. What there is more knowledge of however, is the fate of the polyamines produced in the colon. According to one study, a large fraction appears to enter the bloodstream (>>> study). A link between feces microbiota composition and polyamine levels has also been found (>>> study).
Related to polyamines or not, a >>> study in a short-lived vertebrate found that transfer of “youth” was possible by conducting a gut microbiota transfer from young to middle-aged individuals. Whether the adverse effect of the microbiota in the middleaged individuals is due to a reduction in immunosurveillance capacity (i.e. less ability to keep gut pathogens in check) due to ageing of the immune system or other causes is not clear.
Does fasting keep us young and healthy?
Also, NOT eating is connected to longevity and gut microbiota. So called intermittent fasting was found to lead to life extension and to affect gut health and a more favorable relative bacterial abundance in fruit flies (>>> study). In another >>> study, a so called fasting mimicking diet administered to mice was associated with better outcomes in health, at the same time as changes in the microbiota was observed. It is of no surprise that fasting can lead to changes in the microbiota, but in humans there is no good data that show the effects of fasting per se on the microbiota. It is especially important to compare changes in the human gut microbiota against different background diets. In other words, fasting regimens’ effect on the microbiota could to some degree be the result of the absence of a bad diet (or a good diet for that matter), or changes induced by fasting could be reversed as soon as the fasting period is over.
A good diet is associated with a reduced risk of many diseases and longevity in general, but research into ageing and specific dietary components and characteristics, such as mentioned here, is an exciting starting point for a more nuanced understanding of how diet affects health through the microbiota. And as mentioned in another MyMicrobiome article: The older you get the more important it is to take care of your microbiome.