Younger cells burn fat faster in fasts
A Severe Fast That Rewinds the Body’s Clock
For years, scientists have tracked biological age through epigenetic clocks. These tools measure chemical tags on DNA that change predictably as we grow older. Lifestyle choices like exercise and smoking can alter these patterns too. A recent study tested a 12-day medically supervised fast where volunteers consumed only 200 to 250 calories daily from fruit juice, vegetable broths, and honey. Steve Horvath at the University of California, Los Angeles, led the team that recruited 32 healthy participants aged 25 to 72. They were admitted to a specialist clinic with clinical monitoring throughout. ‘This is not something to try at home,’ Horvath says. The calories were eaten in three windows: 7am to 9am, 11:30am to 1pm, and 6:30pm to 8pm. This schedule pushed the body into a fasting metabolic state, as team member Robin Mesnage at King’s College London explains. That state occurs when the body shifts from burning energy from food to burning energy stored in the body. The researchers used 12 different epigenetic clocks to estimate biological age before, during, and after the fast.
The results were not uniform. Some clocks ticked upward, suggesting the extreme fast placed negative stress on the body. One clock built to detect changes in body mass index went down. These incongruous results between different epigenetic clocks are a known problem in the field. But one finding was fairly consistent across the clocks: participants who entered the study with a younger biological age relative to their chronological age lost more weight than those who were biologically older. Horvath admits the team was not expecting this. ‘Honestly, we don’t know the mechanism,’ he says. The most likely explanation, he thinks, is that biologically younger people have better metabolic adaptability. That means they can switch more swiftly from using food for energy to using stored fat when calories are scarce. Paulina Correa-Burrows at the University of Chile finds this plausible. Biologically younger people tend to have more efficient mitochondria, she says, which enables faster switching to fat burning. They may also have better pathways for sensing nutrients in cells, which could further improve the switch between fuel sources. But Correa-Burrows cautions that the group of volunteers was small, so the results are inconclusive.
A Cellular Switch That Creates New Fat Cells in Midlife
The idea that weight gain with age comes only from existing fat cells getting bigger has dominated textbooks for decades. A study published in the journal Science challenged that assumption. Researchers identified a cellular switch that drives the creation of new fat cells in midlife. They looked at a special category of stem cells called adipocyte progenitor cells, or APCs, found in fat tissue. In youth and early adulthood, these cells stay dormant. But in adults, they have the potential to transform into fat cells and add to the number already present. Scientists used RNA sequencing to study each cell’s gene activity. They took stem cells from very old mice and injected them into the fat tissue of young mice. The number of fat cells in the young mice shot up. Nothing happened when they put stem cells from young mice into other young mice. Something about age was making these APCs become highly active and aggressively start producing new fat cells.
Adolfo Garcia-Ocana, PhD, chair of the department of molecular and cellular endocrinology at City of Hope and study author, explains the finding. ‘While most adult stem cells’ capacity to grow wanes with age, the opposite holds true with APCs,’ he says. ‘Aging unlocks these cells’ power to evolve and spread.’ This is the first evidence that our bellies expand with age due to the APCs’ high output of new fat cells, Garcia-Ocana adds. The scientists also saw that a signaling pathway unique to older mice gave another type of stem cell the go-ahead to create new fat cells, especially around the abdominal area. They replicated the process with human cells and found similar results to what they observed in mice. This discovery opens the door to new types of medications that could keep weight from accumulating. It also means that the hormonal and metabolic changes already known to fuel midlife weight gain — declining testosterone after age 30, the enzyme aromatase in fat tissue that turns testosterone into estrogen, reduced activity levels, and more sleep disorders — are only part of a more complex picture.
Testing Whether the Result Holds Under Gentler Conditions
Horvath now wants to see investigations into whether biologically younger people also lose more weight under less restrictive diets. ‘A 12-day medically supervised fast is not a long-term diet and it isn’t meant to be one,’ he says. The next step is to test if the same advantage for younger biological age appears with diets that are easier to follow and safer to maintain. This would address a major limitation of the current study: the extreme fast cannot be recommended for general use. The team needs to know if the effect is specific to severe calorie restriction or if it applies to more moderate approaches. Until then, Horvath points to habits with the strongest evidence for healthy epigenetic aging. ‘Do not smoke, do physical exercise, keep a healthy body weight and maintain good relationships,’ he says. The findings from both studies suggest that biological age is not fixed. It can be influenced by lifestyle choices that affect the chemical tags on DNA and the behavior of stem cells in fat tissue. The connection between younger biological age and more efficient fat burning during fasting is a new avenue for research, but the practical advice remains familiar. Always speak to a doctor before changing your diet.
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1. DOI: 10.64898/2026.06.12.731903