Super-Ageing takes guts

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, which is looking at ways of modifying disease in old age, and also the first phase of the Frailomic initiative, 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 our diets can reduce the risk of life-shortening comorbidities commonly associated with ageing.  A low-calorie diet appears to reset circadian rhythms, from which comes health and longevity. This is a carrot-and-stick situation for people wanting to stave off ageing – but how much should we reduce our intake and at what age should we start? Human clinical trials involving low-calorie intake are rare so it is difficult to answer these questions. Recently, interest has focused on whether the vast ecosystem of organisms that lives in our digestive systems might be playing more of a role than we suspect. Research has shown our microbiomes to be as complex and influential as our genes in everything from mental health to athleticism and obesity. Weighing in at up to 2kg (heavier than the average brain), scientists are increasingly seeing it as an organ in its own right. Each gut contains about 100 trillion bacteria, many of which play vital roles, breaking down food and toxins, providing vitamins and training 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. 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’. 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 analyzed 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 similar to 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.

This and other studies cannot etablish causality but it is clear there remains a strong and undeniable correlation between a healthy gut and healthy ageing. Exactly how microbes influence lifespan is unclear but one possibility is that immune systems wear out with age, allowing harmful microbes to out-compete more beneficial bacteria. Could we identify common factor that would explain the observations? One  class of chemicals made by intestinal bacteria, known as indoles, certainly seem to help worms, flies and mice maintain mobility and resilience for more of their lifespans. Indole and its chemical relatives can be found in plants, especially vegetables such as broccoli and kale are produced by many types of bacteria through breakdown of the amino acid tryptophan. Researchers have shown that indoles have the potential to make old animals look more like the young ones.

While we wait for the underlying mechanism to be defined we might consider resetting our gut bacteria to those of a 30-year-old and adopting food and lifestyle interventions that ‘may’ promote a longer health spans. What we mean by ‘resetting’ is effectively ‘poop doping’ or undergoing a microbiome transplant. The concept has recently captured the attention of the media and is stimulating public interest. Faecal microbiota transplantation, where faecal matter from a healthy donor is strained and placed in someone else, has been shown to be effective for patients with Clostridium difficile, a serious bacterial infection of the intestines. Serious consideration is now being given to treatment of conditions as wide spread as inflammatory bowel disease, diabetes and obesity as well as 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 in the near future 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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