Is the Gut Microbiome Relevant to Naked Mole-Rat Longevity?

Naked mole-rats live something like nine times longer than similarly-sized rodent species, and appear near immune to cancer. As such they are one of the most studied species among researchers who investigate the comparative biology of aging. Finding the underlying reasons for such large differences may inform human medicine, particularly when it comes to cancer, though in the matter of aging in general there is every chance that this sort of research will be overtaken in relevance in the near term by efforts such as clearance of senescent cells that directly address the root causes of aging. In recent years, it has become clear that gut bacteria have a fair degree of influence over natural variations in longevity in any given mammalian species. It is thus reasonable to ask whether they play a role in naked mole-rat longevity, though it is hard to imagine that this could be a significant contribution in comparison to the cellular differences, which include resilient mitochondrial membrane composition, efficient ribosomes, and overpowered anti-cancer mechanisms.

The composition and functionality of complex and rich community of microbes living on the surfaces and cavities of the mammal's body, i.e. microbiota, is well known to be crucial for the health maintenance of the host. An extremely rich and diverse microbial ecosystem inhabits the gastrointestinal tract collectively named as gut microbiota. Studies on humans have demonstrated that the gut microbiota strongly impacts on the prevention of disorders and pathologies, such as obesity and metabolic syndrome, cardiovascular diseases, inflammatory bowel diseases, as well as several types of cancer. The gut microbiota can indeed influence the education and homeostasis of the immune system and metabolism, as well as brain functionality, with as yet unknown long-term effects on human health and lifespan.

The impact of the gut microbiota on human health is a topic of huge interest for the scientific community, as demonstrated by the ever-increasing amount of studies on the microbiological peculiarities of the human gut ecosystem within the context of different lifestyles, genetic backgrounds, or pathologies. It is a matter of fact that, by preserving the biological homeostasis of the human host, the gut microbiota has a role of primary importance in supporting human longevity. However, only few hypotheses on the mechanisms involved have been advanced. Longevity is a tricky trait to be studied in humans, because it is a rare event, with an incredible amount of confounding genetic, lifestyle, and clinical variables, both past and present. Still, the microbiota of human populations with extraordinary longevity rate is being investigated across geographical zones and interesting hypotheses on the role of the microbiome in health-maintenance during aging are being advanced.

In this scenario, the naked mole-rat might represent an extremely interesting model to study health and longevity, since, like for human beings, in naked mole rat the selection against aging is strongly reduced. This eusocial, subterranean mouse-sized mammal occupies underground mazes of sealed tunnels and lives a very long life in large colonies with only one breeding queen and few breeding males. The naked mole-rat shows few age-related degenerative changes, displays an elevated tolerance to oxidative stress, and its fibroblasts have shown resistance to heavy metals, DNA damaging agents, chemotherapeutics and other poisonous chemicals. Moreover, this mammals show remarkably small susceptibility to both spontaneous cancer and induced tumorigenesis. These features of the naked mole-rat are maintained throughout their long lifespan, making this rodent a putative animal example of impressively prolonged "healthspan".

Moreover, the within-colony low genetic diversity (possibly due to the high inbreeding rate), the climatologically stable underground habitats, and the constant diet (mainly tubers and other underground plant storage organs), make the naked mole-rat a unique model for studying the microbiota-host interaction, focusing on the ability of the gut microbes to contribute to health maintenance during aging. Here, we characterized the gut microbiota of the naked mole-rat by next generation sequencing, aiming at understanding of how the rodent´s gut microbiota profile aligns with human microbiome and that of other mammals.

We found that the naked mole-rat possesses a unique gut microbiome composition, which is the result of the host phylogeny and its peculiar ecology. This microbiome layout has many compositional and functional peculiarities - such as the propensity for an oxidative metabolism, an enhanced capacity to produce short-chain fatty acids and mono- and disaccharides, as well as the peculiar structure within Bacteroidetes, the high load and diversity of Spirochetaceae and the presence of Mogibacteriaceae - some of which are shared with gut microbial ecosystems considered as models of healthy aging, as well as metabolic and immune homeostasis. This might suggest a possible role of the gut microbiota as a universal contributor to mammalian health, which goes beyond the host phylogeny and ecology constrains, supporting health and longevity of the mammalian host.



With everything we are learning about the microbiome, about it's true size, diversity, and integration within the human system, it is a very important target for future discovery

Posted by: Dr. Sal Banetto at September 5th, 2017 6:46 AM

Genetic variation and alliances are important survival strategies in this predator-prey arms race we call evolution. Removing damaging mutations, from our species, would be beneficial but it removes genetic variation and therefore leaves us more vunerable. These alliances can be dangerous and needs constant monitoring. These long lived species, like the Greenland shark, seem to have parcially removed themselves from the evolutionary arms race.

Posted by: Tj Green at September 6th, 2017 6:58 AM

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