Could lithocholic acid-mediated caloric restriction be the key to delaying aging?

Restricting caloric intake has long been associated with improved health and extended lifespan in various species, from yeast to mammals. However, implementing such a regimen often proves difficult due to the accompanying feelings of hunger and energy deprivation. Recent exploration from researchers at Xiamen University in China suggests that lithocholic acid (LCA), a secondary bile acid naturally produced in the gut, might mimic some of the benefits of caloric restriction without the need to drastically cut calorie consumption.

Caloric restriction is known to activate stress response pathways which enhance cellular repair mechanisms, improve metabolic health, and delay the onset of age-related diseases. Yet, these physiological changes come with a trade-off: maintaining a low-calorie diet is challenging, especially in modern environments saturated with calorie-dense foods. This is where LCA enters the picture. “The discovery of LCA as a metabolic mediator of calorie restriction, and its effects across biochemical, cellular, and organismal levels, is truly striking,” says Dr. Xu Chen, an assistant professor at the University of California San Diego.

LCA operates by interacting with key signaling molecules and enzymes involved in energy metabolism. For instance, research has demonstrated its ability to influence the activity of sirtuins, a family of proteins known for their role in longevity. Sirtuins are activated during caloric restriction, leading to improved DNA repair and reduced cellular stress. By mimicking this activation, LCA could provide similar protective effects without requiring individuals to undergo severe caloric deprivation.

A study published in Aging explored the effects of LCA on yeast cells, demonstrating its ability to enhance lifespan by promoting mitochondrial health and reducing oxidative damage. Studies have revealed that LCA can extend the lifespan of yeast by activating similar cellular pathways as caloric restriction, such as those related to improving/maintaining mitochondrial function and decreasing oxidative stress. Mitochondria, often referred to as the “powerhouses” of the cell, play a crucial role in determining an organism’s energy efficiency and susceptibility to age-related diseases. LCA’s ability to optimize mitochondrial function makes it a compelling candidate for further exploration in human health and aging.

While these findings are promising, translating results from model organisms like yeast to humans remains a complex task. The human microbiome’s ability to produce LCA varies significantly between individuals, influenced by factors such as diet, genetics, and overall gut health. Future studies may explore whether dietary interventions or probiotic approaches are capable of enhancing natural LCA production. Additionally, the long-term effects of LCA supplementation on humans have yet to be thoroughly studied. Researchers caution against assuming that LCA can act as a “silver bullet” for aging without understanding its broader implications on human metabolism.

“The work is incredibly comprehensive. I think this will break open a whole new branch of research based on gut microbiome byproducts and aging,” explains Dr. Marc Tatar, a professor at Brown University. 

Despite the challenges ahead, the discovery of LCA’s role in mimicking caloric restriction opens a new avenue in aging and metabolic research. If further studies confirm its effectiveness and safety in humans, LCA-based therapies could offer a practical alternative to caloric restriction, benefiting those at risk of age-related conditions such as diabetes, cardiovascular diseases, and neurodegenerative disorders.

In a world where longevity and healthspan are becoming increasingly prioritized, lithocholic acid may emerge as a key player in bridging the gap between scientific discoveries and everyday wellness. As advancements in understanding LCA’s mechanisms continue, the scientific community creeps closer to achieving the perpetual goal of healthy aging.