Fight Aging!

The gut microbiome changes with age in a number of different ways that are detrimental to long term health. Firstly, inflammatory microbial populations increase in number, rousing the immune system to constant overactivation. Secondly, microbial populations capable of generating beneficial metabolites such as butyrate are reduced in number. Researchers here present additional evidence for the importance of reduced butyrate production in mouse aging. As it is possible to favorably adjust the gut microbiome via a number of strategies (such as fecal microbiota transplantation, flagellin immunization, and, in principle at least, suitable probiotics), this is an area of research to keep an eye on.

Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing of young and old mice, injection of young serum into old mice, and parabiosis between young and old mice. Ageing-induced changes in the composition of the gut microbiota are associated with various age-related disorders. However, the rejuvenating effects of altered gut microbiota on the presence of specific bacteria remain elusive. Here, we show the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia muciniphila (AK).

Our results indicate that intestinal function, inflammation, and intestinal homeostasis of aged mice can be rescued by three rejuvenation intervention models. All rejuvenation procedures significantly increased the relative abundance of the butyrate producer Oscillospira in rejuvenated mice, while the abundance of the beneficial genus Akkermansia was significantly increased in rejuvenated mice only during co-housing and serum injection. In addition, we observed that the abundance of aged-specific genera, such as Paraprevotella, Prevotella, Odoribacter, Erysipelotrichaceae cc_115, Rikenellaceae AF12, and Helicobacter, was significantly decreased in all rejuvenated mice, suggesting that the relative abundance of young- and aged-specific bacteria was reversed in their young counterparts during the co-housing and parabiosis procedures.

It has been reported that a high abundance of Prevotella, Turicibacter, and Paraprevotella is associated with dysbiosis, chronic inflammation, and type 2 diabetes, suggesting that they increase the risk of inflammation. Defective intestinal function and inflammation in aged mice can be improved by gut microbiota remodelling, suggesting a causal link between age-related changes in the gut microbiome and age-dependent morbidities.

For effective anti-ageing, it is important to find an appropriate approach to specifically manipulate the microbiota. Although fecal microbiota transplantation has shown potential in the treatment of several diseases, it is a complex biological intervention and has intrinsic limitations, that is, it can use only feces from healthy donors that are free from diseases. In this study, we controlled the ageing-related phenotype by oral administration of a single microbe, AK. AK restores intestinal integrity by activating epithelial cells, thereby supporting the growth of other beneficial commensals.

Furthermore, our data shows that AK extends the healthy lifespan, as evidenced by the frailty index and restoration of muscle atrophy. Since the age-related inflammatory state is associated with a decrease in skeletal muscle size and function (sarcopenia), the decrease in inflammation caused by oral administration of AK may be involved in the restoration of muscle metabolic function.

Link: https://doi.org/10.1186/s40168-021-01189-5