An Example of the Importance of Gut Microbiota to Aging in Flies

If we paint with very broad strokes, we can say that flies generally die from intestinal failure in the same way that humans generally die from cardiovascular failure. For flies, the intestine is at the center of the mechanisms determining the pace and manifestations of aging in that species, and the cause of a majority of deaths. While being far from the only organ to consider in fly aging, it does appear to take center stage. Bear this in mind while looking at the research noted here.

All in all, it isn't too surprising to hear that researchers have been able to demonstrate a 60% life extension in flies through a method that involves suppressing some of the detrimental age-related changes in gut bacteria. (Though it appears that almost everything else of interest to the aging process in metabolism is also adjusted via the approach taken here - which makes it hard to ascribe the outcome to any one specific item). In recent years the research community has given ever more attention to the activities of the microbial population of the intestines in various species including our own. Evidence suggests thatthe way in which populations of gut bacteria change over a life span are influential in aging to a degree that may be in the same ballpark as, say, exercise or other noteworthy environmental factors.

Nonetheless, I think caution is wise when extrapolating any research of this nature carried out in flies, given the enormous importance of intestinal function in fly aging. It would be logical to expect to find similar effects in mammals, but nowhere near as large in their consequences. The intestine doesn't seem as central to aging in mammals as it is in flies: the importance of various organs and bodily systems shifts and becomes more distributed as one moves from lower to higher animals. Quite aside from this, we should remember that there are many ways to significantly extend life in short-lived species such as flies that (a) touch on the mechanisms affected here, and (b) are known to do little for human longevity. Large numbers in life extension mean little on their own when demonstrated in worms, flies, and the like.

When thinking about the mechanisms involved in the connection between gut bacteria and aging, inflammation is likely one of the most important. Gut microbes interact with the immune system, and some are more capable of provoking inflammatory reactions. If, for reasons relating to the many complex changes in lifestyle and immune function and other tissues that occur with age, more inflammatory bacteria come to dominate, then that will cause harm over the long term. There are, however, a growing number of other more subtle mechanisms to consider. Given the comparative recency of this part of the field of aging research, it is fair to say that much remains to be discovered.

The secret to longevity is in the microbiome and the gut

Scientists fed fruit flies with a combination of probiotics and an herbal supplement called Triphala that was able to prolong the flies' longevity by 60% and protect them against chronic diseases associated with aging. The study adds to a growing body of evidence of the influence that gut bacteria can have on health. The researchers incorporated a synbiotic - made of probiotics with a polyphenol-rich supplement - into the diet of fruit flies. The flies fed with the synbiotic lived up to 66 days old - 26 days more than the ones without the supplement. They also showed reduced traits of aging, such as mounting insulin resistance, inflammation, and oxidative stress.

"Probiotics dramatically change the architecture of the gut microbiota, not only in its composition but also in respect to how the foods that we eat are metabolized. This allows a single probiotic formulation to simultaneously act on several biochemical signaling pathways to elicit broad beneficial physiological effects, and explains why the single formulation we present in this paper has such a dramatic effect on so many different markers. The effects in humans would likely not be as dramatic, but our results definitely suggest that a diet specifically incorporating Triphala along with these probiotics will promote a long and healthy life."

The findings can be explained by the "gut-brain axis," a bidirectional communication system between microorganisms residing in the gastrointestinal tract - the microbiota - and the brain. In the past few years, studies have shown the gut-brain axis to be involved in neuropathological changes and a variety of conditions such as irritable bowel syndrome, neurodegeneration, and even depression. Few studies, however, have successfully designed gut microbiota-modulating therapeutics having effects as potent or broad as the formulation presented in the new study.

Longevity extension in Drosophila through gut-brain communication

The gut microbiota is complex ecosystem of bacteria, fungi, and microorganisms residing in the gastrointestinal tract, which impart many health benefits onto the host. Distinct variations in the composition of the gut microbiota in the elderly have been identified and could contribute to frailty, disease development and aging itself. A diet rich in probiotics and prebiotics may help prevent chronic age-related disease. Changes in the gut microbiota of aging individuals has a high inter-individual variability due to disease manifestation, medication, diet, and environmental exposure.

In general, aging subjects have a decline in the phyla Firmicutes, elevation in Bacteriodetes, reduction of Bifidobacteria, elevation in the proinflammatory Proteobacteria accompanied by a decline in overall diversity, which is associated with various health risks and fraility. Indeed, a general decrease in the level of short-chain fatty acids (SCFAs) is apparent in aging individuals which is linked to inflammation and adipose tissue dysregulation.

The gut-brain-axis (GBA) is a bidirectional communication system between the gastrointestinal tract microbiota and the brain including various metabolic, immunological, endocrine, and neuronal signals derived from individual bacterial cells and their metabolites. Through this axis, the gut microbiota was recently identified as a target for therapeutic intervention against age-related diseases. For example, several probiotic bacteria have shown beneficial effects in managing symptoms of neurodegeneration.

The present study describes how a novel probiotic and synbiotic formulation impacts Drosophila melanogaster longevity through mechanisms of the GBA. It was previously shown that the probiotic and synbiotic formulation used in the present study has beneficial effects on aging. The present probiotic and synbiotic formulations showed combinatorial action on reducing markers of physiological stress, oxidative stress, inflammation and mitochondrial electron transport chain complex integrity therefore targeting most of the main aging mechanisms. This action benefits not only longevity but would prevent many age-related chronic diseases that are associated with the aforementioned states.

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