Why This Matters to Us:
As longevity enthusiasts, we are always excited about research that explores interventions for healthy ageing. Calorie restriction is one of the most well-studied methods for extending healthspan and potentially lifespan across multiple species, but it isn’t practical for everyone. Studies like this give us new ways to understand why calorie restriction works—and whether its benefits can be duplicated without drastically reducing caloric intake. Lithocholic acid (LCA), a bile acid identified as a key player in the latest study, could someday offer ageing-related health benefits as part of a new class of treatments called calorie restriction mimetics. This research could open the door to easier, scientifically-backed ways to live longer and healthier lives.
The Detail:
Calorie restriction (CR), where an individual reduces their daily food intake by about 30% without suffering malnutrition, is known to deliver remarkable anti-ageing benefits. Research has shown that CR prolongs lifespan in animal models like mice and monkeys, while also improving health by addressing conditions such as obesity, frailty, and insulin resistance in humans. However, the molecular mechanisms behind these changes remain unclear. Identifying these mechanisms could help scientists develop new treatments that mimic CR’s effects without requiring people to restrict their diets drastically.
In a study recently published in Nature, researchers from Xiamen University in China focused on a bile acid called lithocholic acid (LCA). They found that this molecule acts as a potential calorie restriction mimetic. In simple terms, this means LCA could mimic some of the health and anti-ageing effects triggered by calorie restriction. LCA is naturally produced in the gut when certain bacteria synthesise it using precursors released from the liver, but a CR diet significantly increases its levels in the bloodstream.
The study revealed that the amount of LCA in the blood rises by about fivefold after just two weeks of calorie restriction. Interestingly, after examining hundreds of metabolites—substances created or altered by bodily processes—LCA stood out as one with the greatest potential. It was the only metabolite identified that both increased with CR and strongly activated a protein called AMPK. AMPK is often referred to as the body’s energy “switch.” It plays a crucial role in regulating cellular energy, promoting healthy metabolism, and protecting cells from damage—all of which are important for healthy ageing. The elevated LCA levels and resulting AMPK activation may explain part of calorie restriction’s impressive effects.
Lin and his colleagues wanted to find out if giving LCA directly to animals could replicate the benefits of calorie restriction. They tested it on aged mice, observing several positive health effects. Like calorie restriction, LCA improved insulin sensitivity, increased NAD+ levels (a molecule associated with energy production and cellular repair), and enhanced grip strength, a measure of physical function. Together, these benefits suggest that LCA could help extend the “healthspan,” the productive years of life free from disease, even if it doesn’t significantly increase lifespan in all cases.
However, lifespan results varied. While LCA significantly extended the lifespan of roundworms and fruit flies, its effects on mice were less consistent. In one group of mice treated with LCA, males lived about 5% longer than usual, and females lived about 10% longer. These results did not reach statistical significance due to variability between groups and dosage levels, but they hint at LCA’s potential longevity benefits if further refined.
Another major takeaway from this research is the connection between gut bacteria and LCA production. Some gut bacteria, including Lactobacillus, Clostridium, and Eubacterium, are responsible for producing LCA from precursors in the liver. The study raises the exciting possibility that we could enhance LCA’s benefits through dietary changes or probiotics that increase the abundance of these LCA-producing bacteria. In this way, the gut microbiome might play a larger role in how calorie restriction promotes longevity.
It’s important to note that while the findings are promising, more research is needed. For example, the mice in this study only began receiving LCA at one year of age, and it’s possible that starting treatment earlier or adjusting the dosage could deliver stronger effects. Similarly, scientists will want to explore how well LCA works in humans before it’s considered a viable treatment.
Does this mean you should start fasting or try to boost your LCA levels immediately? Not yet. Although this study holds a great deal of promise, the results are still in the preliminary stages. Current research shows that lifestyle changes such as a healthy diet, exercise, and maintaining a balanced microbiome are some of the best tools available for improving healthspan.
Final Thoughts:
This study sheds light on the mechanisms that make calorie restriction a remarkable tool for improving health. Lithocholic acid (LCA) offers a promising path toward replicating these benefits in a more accessible way. Whether through new treatments, microbiome interventions, or dietary changes, LCA could play a significant role in shaping the future of longevity science. For now, though, staying updated on cutting-edge research like this strengthens our understanding of how to live longer, healthier lives.