Longevity Briefs: Can Intermittent Fasting Keep Your Stem Cells Young?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

As we age, our bodies undergo a natural decline in the function of cells, tissues and organs, leading to various health issues and chronic diseases of ageing. One of the hallmarks of ageing is stem cell exhaustion – stem cells, whose main purpose is to divide and develop into specialised cells to replace those that are naturally lost over time, fail to properly fulfil this function in old age. Stem cell exhaustion is itself the consequence of more fundamental biological changes, but anything we can do to preserve healthy stem cell populations in old age should in theory translate to wide ranging health benefits.

One example of the importance of a healthy stem cell population is in the inner lining of the gut – the intestinal mucosa. The cells of this lining must be replaced every 3-5 days – one of the highest turnover rates in the body – relying on intestinal stem cells (ISCs) constantly generating new cells to replace those that are lost. Previous studies suggest that these cells may be particularly sensitive to diet, with some diets able to negatively impact ISC function. In this study, researchers investigate how intermittent fasting impacts ISCs in animal models. Sharp reductions in calorie intake have been found to extend lifespan in many animals by affecting some of the biological processes that are fundamental to ageing. Practices like intermittent fasting seem to have greater lifespan-extending effects in shorter-lived organisms, and may not extend lifespan in humans at all, but are still likely to have some significant health benefits.

The discovery:

Researchers chose to conduct their study in African turquoise killifish (Nothobranchius furzeri). They chose this as their model organism because of the killifish’s short lifespan, allowing them to observe age-related changes quickly. They divided 10 adult fish (10 weeks old) into two equal groups: one group received food ad libitum, meaning they could eat as much as they wanted, while the other group underwent intermittent fasting (IF), specifically an “alternate-day fasting” regimen, where they were fed every other day.

ISCs in the intestines of the killifish were studied throughout their lives. Researchers found that the cycle time of these stem cells increased with age (stem cells took longer to replicate), and the overall intestinal length and volume decreased. This was accompanied by changes in gene expression. Genes related to stem cell maintenance and to circadian rhythm (the cell’s internal ‘clock’) were altered, but many of these changes did not occur in the old killifish that had undergone intermittent fasting. The expression levels of genes – including those involved in cell differentiation, stem cell function, nutrient absorption, and mitochondrial health – resembled those of younger, adult fish. This suggested that intermittent fasting may have counteracted ISC ageing, although unfortunately the researchers did not confirm whether actual cell cycle time was affected.

The implications:

This research suggests that intermittent fasting can effectively reverse age-related gene expression patterns in the intestine, helping to maintain a more “youthful” population of intestinal stem cells, which should translate to a healthier gut in general. While killifish may have very short lifespans, their intestinal mucosae do share some fundamental similarities to our own. There have also been other studies in other animal models suggesting that fasting can benefit mucosal health during ageing. It’s not much of a stretch to suggest that intermittent fasting and other methods of calorie restriction may preserve the function of human ISCs.