The microbial gatekeepers of immortality

old man Neil Moralee 1024w 12243870446_4f24d7e2a9_bWhen you look in the mirror, you see a reflection of yourself: your eyes, your hair, your body, all the result of the translation of the information encoded in your genes. What you don’t see are the trillions of microorganisms you are host to, which are key contributors to what makes you you.

We now know that these microorganisms, and the genes that they encode (the microbiome), have a key role in shaping you, their host, with effects ranging from your ability to ward off pathogens, to your metabolism and even your development and mental health. Research in the past few years has highlighted that they may also form part of the puzzle that answers one of the age-old questions: why (and how) do we grow old?

Like with many problems in biology, researchers have turned to invertebrate model organisms, specifically the worm C. elegans and the fruitfly D. melanogaster, for clues on a role for microorganisms (and specifically those living in the gut, known as the gut microbiota) in ageing. These organisms – which gave us the first insights into the molecular regulation of ageing, including the role of the insulin signalling pathway – offer the advantage of having short lifespans and being genetically controllable.

Intriguingly, for both organisms the presence or absence of bacteria has been shown to have a considerable effect on lifespan, through direct or indirect effects on the expression of longevity genes. However, the story is far from simple. In the case of C. elegans, for instance, some bacterial signals, such as the metabolite nitric oxide, increase the worms’ lifespan. By contrast, others decrease it, for example the small non-coding RNA DsrA. Moreover, different bacteria species themselves can differentially influence the worms’ longevity.

So, although an effect on ageing is evident, we still have some way to go before we can truly understand exactly how the gut microbiota influences longevity. We also don’t know if any of the observations made in invertebrates will translate to mammals, and humans in particular.

Despite this, researchers have observed a link between changes in the gut microbiota and ageing in humans. This, of course, should not come as a surprise; diet is a key influencer of gut microbiota composition, and for many of us unfortunately old age is accompanied with health problems that could affect our diet, commonly dental issues and muscle weakening.

old lady in market_christingO_1024w 12821646714_11abd214a2_bFurther clues have come from a group working on the ELDERMET project, an initiative funded by the Irish Government that studies the relationship between diet, health and the gut microbiota in the over 65s. In 2012, the group published a seminal study identifying a link between the composition of the gut microbiota in the elderly and their diet and health status. Like with all microbiome research, they were not able to prove causality but the correlation was clear: the frailest elderly individuals, who lived in care homes and ate a diet high in fat and low in fibre, had an altered gut microbiota composition compared with those who were healthy. As the researchers put it: “the healthiest people live in a community setting, eat differently and have a distinct microbiota from those in long-term residential care.”

This offers an opportunity: by understanding how the diets, and by inference the gut microbiota, of healthy and frail elderly individuals differ, we might be able to come up with interventions that ensure that we have a long and healthy old age (for example, through a high-fibre diet). Indeed, the ELDERMET group is now part of a larger initiative called NU-AGE, which is looking more broadly into how changes in diet can influence the ageing process.

We are still at the beginning of our exploration of the tangled web that is our interaction with our microbial friends, and of the effects they have on our longevity. But what is so far clear is that our view of the ageing process needs to be more holistic; we are part of a ‘superorganism’ comprising both our genome and that of our microbiota, and therefore any intervention, whether to promote lifespan or healthspan, needs to take us both into consideration.

This is online-only content relating to the Autumn 2014 iScience magazine #29 themed on ‘Time’.  Read the magazine; other online-only content.  Images from Flickr under Creative Commons license (Top: The old man and the sea, Neil Moralee; Bottom image: Marche, Christine Vaufrey)

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