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Gut Microbes of Old Rats Cause Cognitive Decline in Young Rats

Researchers have demonstrated that age-related cognitive impairment and inflammation can be caused in young rats simply by giving them gut microbe populations from the guts of aged rats.

The gut microbiome

The microbiome describes the varied community of bacteria, archaea, eukarya, and viruses that inhabit our gut. The four bacterial phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria comprise 98% of the intestinal microbiome.

The microbiome community is a complex ecosystem whose activity regulates a number of functions in the gut and interacts with the immune system and energy metabolism. The beneficial bacteria in our gut also help to prevent the growth of harmful bacteria, protect us from invasive microorganisms, and help to maintain the integrity of the intestinal barrier.



Building on existing evidence

Building on the evidence for the role of the gut microbiome in aging, this new study shows that the age-related changes to the microbiome contribute to cognitive decline in aged rats [1].

The study is particularly noteworthy because it is one of several similar, recent studies that explore age-related changes to the gut microbiome by using fecal transplants from old to young animals. During the experiment, the young rats that received the fecal transplants, which shifted their microbiome towards that of aged rats, experienced impaired cognition as a result.

Also of note is the increased presence of advanced glycation end products (AGEs), which are harmful compounds created when proteins or fats combine with sugars in the bloodstream in a process known as glycation. Some researchers propose that the accumulation of AGEs is a reason we age, and there is certainly some evidence to support this hypothesis.

These study results once again suggest that cognitive impairment is the result of the age-related changes to the microbiome and that this is mediated by chronic inflammation. There is increasing support for the idea that inflammaging, the chronic smoldering background of inflammation typically present in older people, may originate in the microbiome, and this study adds further fuel to the fire.

Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.

Conclusion

Given the evidence to date, it seems clear that changes to the microbiome during aging are closely linked to detrimental changes to health. Restoring the microbiome so that it is similar to that of younger individuals could be a potential strategy for supporting healthy longevity. Fecal microbiota transplantation is a reasonably low-tech and translatable approach that could potentially achieve this goal.

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Literature

[1] Zhang, C., Guo, D., Wu, S., Yin, L., Yang, X., Zhao, X., … & Yin, Y. (2020). Age-related shifts in gut microbiota contribute to cognitive decline in aged rats. Aging, 12.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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