Super-ageing takes guts

September 28, 2017

- Tim Hardman

We are looking over the precipice that is a revolution in lifespan modification. Some of us seem to be experiencing the benefits already. Super-ager is a term that refers to people in their 80s (and older) who have the mental or physical capability of their decades-younger counterparts.

It is universally agreed that over the last 150 years access to sanitation, waste removal, electricity, refrigerators, vaccinations and our constant improvements in healthcare have been responsible for increases in average population life expectancy. Factors such as exercise, diet and smoking cessation coupled with education and mental health have been identified in the last 25 years as lifestyle factors that we can modify to not only further extend our lifespan but also counter the inevitable effects of ageing on health. Much of our understanding of the ageing process has been achieved by research conducted in the elderly. In this brief series by taking a snapshot of current development in the science of ageing we mark the conclusion of the clinical phase of the MID-Frail study [1], a major new international research study examining the effectiveness of combining optimised medical management with exercise and dietary programmes to maintain function and quality of life in people aged over 70 years who have Type 2 diabetes, and the first phase of the Frailomic initiative [2], investigating inherent markers for the development of frailty. Both initiatives are funded by multimillion Euro grants from the European FP7 Framework and being run by Niche Science & Technology Ltd.

We are what we eat, and the foods we eat can lower the chance of getting diseases that shorten life that are common with getting older. It looks like a low-calorie diet can reset circadian rhythms, which is good for your health and makes you live longer. For people who want to delay ageing, this is a "carrot and stick" situation. But how much should we cut back on our intake, and when should we start? It is hard to answer these questions because low-calorie diets aren't often used in human clinical studies. Recently, people have been wondering if the huge community of living things in our gut systems might be more important than we think. Researchers have found that our microbiomes are just as complicated and important as our genes when it comes to everything from our mental health to our weight and fitness. Scientists are starting to see it as its own organ because it can weigh up to 2 kg, which is more than the normal brain. About 100 trillion bacteria live in our guts. Many of them are very important because they break down food and toxins, give us vitamins, and train our immune systems.

Certainly, recent evidence from animal studies appears to support the involvement of the microbiome in ageing. As they age, humans and mice tend to lose a degree of the diversity in their microbiomes, expressing a more uniform community of gut microbes, with once-rare and pathogenic species rising to dominance. Recently, researchers have shown that older fish live longer after they consumed microbes from the pooh of younger fish [3]. The turquoise killifish (Nothobranchius furzeri) inhabits short-lived ponds that form during rainy seasons in Mozambique and Zimbabwe. It is has a very brief existence, reaching sexual maturity at 3 weeks old and dying within a few months. It may not be the most appetizing way to extend life, but when gut microbes were transplanted from young to middle-aged fish it dramatically affected their longevity more than 40%.

This observation appears to reflect what we have seen in human studies, where extremely healthy seniors have the same bacterial composition in their guts as healthy 30-year-olds. In a recent study, participants were selected based on criteria of ‘extreme health’ [4]. These included no reported disease, either in themselves or in their family. They also didn’t smoke, nor did they consume any alcohol, had no reported moodiness, and had not been prescribed any drugs or antibiotics in the 3 months leading up to the study. They also had no family history of major cardiometabolic, gastrointestinal, or neurological diseases. The scientists analysed the gut microbiota of more than 1,000 very healthy individuals aged between 3 and 100 years. Gene sequencing showed that the overall microbiota composition of the healthy aged group was like that of people decades younger. In addition, the major differences between groups in the gut microbiota profiles developed before they reached 20, with gut microbiota differing little between individuals from the ages of 30 to >100. The authors speculated that the similarity between the very fit elderly and 30-year-olds was a consequence of an active, healthy lifestyle and diet.

There is a strong and undeniable link between a healthy gut and good ageing, even though this and other studies can't prove cause and effect. It's not clear exactly how microbes affect lifespan, but one idea is that immune systems weaken with age, letting harmful microbes beat out more helpful bacteria. Could we find a factor that all the findings have in common that would explain them? Undulating bacteria in the gut make a group of chemicals called indoles. These chemicals help worms, flies, and mice stay mobile and strong for longer. Many types of bacteria break down the amino acid tryptophan to make indole and chemicals that are related to it. You can find these chemicals in plants, especially veggies like broccoli and kale. They have shown that indoles can make old animals look more like they do when they are young.

While we wait for the underlying mechanism to be figured out, we might think about changing our gut bacteria to those of a 30-year-old and making changes to our diet and habits that "may" help us live longer. When we say "reset," we really mean "poop doping" or getting a microbiome transfer. The idea has recently gotten a lot of attention from the media, which is making people interested. To help people with Clostridium difficile, a dangerous bacterial illness of the intestines, faecal microbiota transplantation has been shown to work. This is when faeces from a healthy donor is strained and put into someone else. Now, people are really thinking about how to treat diseases like inflammatory bowel disease, diabetes, obesity, and even depression.

The thought of undergoing what might politely be called a ‘reverse enema’ with someone else’s pooh could be distasteful to many. But there remains the possibility that your own microbiome, sampled and preserved early in life, could have the same impact on health and lifespan when reintroduced later. It may be that soon we will come to realise that the fountain of youth will look more like something Sir Joseph Bazalgette would design than the fountains at Versailles.

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