Gut Microbes from Younger Killifish Extend Life in Older Killifish

The research I'll point out today is interesting, but should probably be filed away for later consideration once the mechanisms involved are better understood. Researchers have found that delivering the gut microbes of young killifish to older killifish extends the life span of those older fish. This has echoes of parabiosis experiments in mice, linking younger and older animals together, in the sense that it might shine some light on the impact of specific changes that occur over the course of aging. The study takes place in the broader context of recent data that suggests the microbial population of the gut changes significantly with aging, and that gut microbes have a fair-sized influence on health. This might be via modulation of nutrient update, already an important factor in the life span of short-lived species, via interaction with the immune system, or via any number of other still poorly explored or yet to be cataloged mechanisms. It is a young area of research, with a great deal left to explore.

Is the research community likely to generate methods of manipulating the mammalian gut microbiome that produce better results for human long-term health than, say, calorie restriction or exercise? Outside of fixing a range of uncommon medical conditions that turn out to be due entirely or in large part to errant microbes in the gut, I'd say large gains in human healthspan are not all that plausible. There are already a great many ways to influence the gut microbiome, including the aforementioned practice of calorie restriction, and the observed impact of these strategies puts some limits on what it is plausible to expect from a more rigorous, informed, and technologically assisted adjustment of this microbial population. As always, when looking at these results bear in mind that short-lived species have a far greater plasticity of longevity - when compared against humans - when it comes to this sort of intervention. Methods such as calorie restriction, that extend life in mice by 40% or more, are certainly nowhere near as beneficial in humans.

'Young poo' makes aged fish live longer

It may not be the most appetizing way to extend life, but researchers have shown for the first time that older fish live longer after they consumed microbes from the poo of younger fish. So-called 'young blood' experiments that join the circulatory systems of two rats - one young and the other old - have found that factors coursing through the veins of young rodents can improve the health and longevity of older animals. But the new first-of-its-kind study examined the effects of 'transplanting' gut microbiomes on longevity. It is anticipated that scientists will test whether such microbiome transplants can extend lifespan in other animals.

Life is fleeting for killifish, one of the shortest-lived vertebrates on Earth: the fish hits sexual maturity at three weeks old and dies within a few months. Previous studies have hinted at a link between the microbiome and ageing in a range of animals. As they age, humans and mice tend to lose some of the diversity in their microbiomes, developing a more uniform community of gut microbes, with once-rare and pathogenic species rising to dominance in older individuals. The same pattern holds true in killifish, whose gut microbiomes at a young age are nearly as diverse as those of mice and humans.

To test whether the changes in the microbiome had a role in ageing, researchers 'transplanted' the gut microbes from 6-week-old killifish into middle-aged 9.5-week-old fish. They first treated the middle-aged fish with antibiotics to clear out their gut flora, then placed them in a sterile aquarium containing the gut contents of young fish for 12 hours. Killifish don't usually eat faeces, but they would probe and bite at the gut contents to see whether it was food, ingesting microbes in the process. The transplanted microbes successfully recolonized the guts of the fish that received them, the team found. At 16 weeks of age, the gut microbiomes of middle-aged fish that received 'young microbes' still resembled those of 6-week-old fish.

The young microbiome 'transplant' also had dramatic effects on the longevity of fish that got them: their median lifespans were 41% longer than fish exposed to microbes from middle-aged animals, and 37% longer than fish that received no treatment (antibiotics alone also lengthened lifespan, but to a lesser extent). And at 16 weeks - old age, by killifish standards - the individuals that received young gut microbes darted around their tanks more frequently than other elderly fish, with activity levels more like 6-week-old fish. By contrast, gut microbes from older fish had no effect on the lifespans of younger fish. Exactly how microbes influence lifespan is hazy. "The challenge with all of these experiments is going to be to dissect the mechanism. I expect it will be very complex."

Regulation of Life Span by the Gut Microbiota in The Short-Lived African Turquoise Killifish

Gut bacteria occupy the interface between the organism and the external environment, contributing to homeostasis and disease. Yet, the causal role of the gut microbiota during host aging is largely unexplored. Here, using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, we show that the gut microbiota plays a key role in modulating vertebrate life span. Recolonizing the gut of middle-age individuals with bacteria from young donors resulted in life span extension and delayed behavioral decline. This intervention prevented the decrease in microbial diversity associated with host aging and maintained a young-like gut bacterial community, characterized by overrepresentation of the key genera Exiguobacterium, Planococcus, Propionigenium and Psychrobacter. Our findings demonstrate that the natural microbial gut community of young individuals can causally induce long-lasting beneficial systemic effects that lead to life span extension in a vertebrate model.

Comments

The big story here is that the poop-derived bacteria was placed in an aquarium for universal transfer to all of the killifish. Put on your utopian thinking cap. Instill water supplies or foodstuffs with this bacterial broth and you could theoretically produce universal longevity, no anti-aging pills needed. Not anticipated any time soon, however.

Posted by: Bill Sardi at April 9th, 2017 8:39 AM

Thanks for this update. Doing a lot on MGB axis and I knew it was only time when we would apply this to aging. Unfortunately, I'm not funded to do this but I will add it to my exploration. Did they do any deep sequencing? Tha twe could offer
Mark

Posted by: Dr. Mark Obrenovich. at April 10th, 2017 7:37 PM

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