Biological rejuvenation has the potential to lower the risks of cardiovascular diseases, cancer, and dementia. According to a new discovery, whose findings were published on the preprint server bioRxiv, this process might also aid in weight loss, possibly by improving how efficiently the body switches from using food as an energy source to utilizing stored fat.
In February, a review of existing studies concluded that intermittent fasting—such as the 5:2 diet, where you eat normally for five days a week and limit calories on the other two—is likely no more effective for weight loss than doing nothing at all. However, fasting can also involve abstaining from food or consuming very small amounts over a single continuous period, sometimes done for religious reasons.
Focusing on this latter type of fasting, Steve Horvath from the University of California, Los Angeles, and his colleagues recruited 32 volunteers with no known health issues. These individuals consumed only 200–250 calories per day through fruit juices, vegetable broths, and honey for 12 days. “This isn’t something to try at home,” says Horvath. “It was an inpatient program under medical supervision in a specialized clinic, with continuous clinical monitoring.”
Calorie intake occurred during three time windows: from 7:00 to 9:00, from 11:30 to 13:00, and from 18:30 to 20:00. This placed the participants—aged between 25 and 72—into a state of fasting metabolism, according to team member Robin Mesnage from King’s College London. This state arises when the body shifts from burning energy derived from food to using energy stored within the body.
The team employed 12 different epigenetic clocks to assess and track the volunteers’ biological age throughout the study. These clocks primarily work by analyzing patterns of chemical marks on DNA, which change predictably with age but can also be influenced by lifestyle factors, such as physical activity levels.
The clocks’ responses to fasting varied. Some indicated an older age, suggesting that extreme fasting had a negative impact on the body. However, one of the “epigenetic clocks,” designed to track changes in body mass index, malfunctioned.
Inconsistent results are a known issue when using different epigenetic clocks. Yet, one finding was quite consistent: participants who were initially considered to have a younger biological age relative to their chronological age lost more weight than those who were biologically older.
According to Horvath, the researchers did not anticipate this outcome. “Honestly, we don’t understand the mechanism,” he says. But he believes the most likely explanation is that biologically younger individuals possess better metabolic adaptability, meaning they can quickly switch from using food as an energy source to relying on stored fat when calories are scarce.
This is plausible because biologically younger people tend to have more efficient mitochondria, leading to a faster shift toward fat burning, says Paulina Correa-Burrows from the University of Chile.
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Biologically younger individuals may also have more advanced mechanisms for sensing nutrients within cells, which could further enable a more efficient switch between energy sources for fat burning. However, Correa-Burrows cautions that the volunteer group was small, so the results are inconclusive.
Horvath now wants to conduct studies to determine whether biologically younger people lose more weight on less restrictive diets. “A 12-day medically supervised fast is not a long-term diet, and it isn’t intended to be one,” he says.
In the meantime, a healthy lifestyle can help reduce our biological age. “The habits with the most compelling evidence for healthy epigenetic aging are the well-known ones: not smoking, exercising, maintaining a healthy weight, and fostering good relationships,” says Horvath.
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