Research
Fasting interventions become less effective with age, study finds

Fasting interventions, which involve alternating periods of fasting and refeeding, are generally thought to improve health. But these interventions don’t work as well in old animals, according to a study on killfish.
By studying the short-lived killifish, researchers at the Max Planck Institute for Biology of Ageing in Cologne have shown that older fish deviate from a youthful fasting and refeeding cycle, and instead enter a state of perpetual fasting, even when ingesting food.
It has already been shown in many model organisms that a reduced diet, either through calorie restriction or periods of fasting, has a positive effect on health.
Researchers introduced fasting interventions at different ages, finding that these interventions in older age do not yield the same benefits as they do in younger animals.
A team of scientists from Cologne, Germany investigated the age-related fasting effects in killifish. Killifish are rapid-aging fish that go from young to old in just a few months.
The researchers either fasted young and old fish for a few days or fed them twice a day. They found that the visceral adipose (fat) tissue of old fish became less responsive to feeding.
“The adipose tissue is known to react most strongly to variations in food intake and has an important role in metabolism. That’s why we looked at it more closely,” said Roberto Ripa, lead author of the study.
The researchers found that the inability to respond to the feeding phase set the fat tissue of old fish in a permanent state of fasting: energy metabolism is shut down, protein production is reduced, and tissue is not renewed.
“We had assumed that old fish would not be able to switch to fasting after feeding. Surprisingly, the opposite was true, the old fish were in a permanent fasting state, even while eating food,” said Adam Antebi, Director at the Max Planck Institute for Biology of Ageing and leader of the study.
When the researchers looked more closely at how the fatty tissue of the old fish differed from that of the young, they came across a specific protein called AMP kinase. This kinase is a cellular energy sensor and is made up of different subunits, one of which decreases with age.
When the scientists increased the activity of this subunit through genetic modification, the fasting-like state was counteracted and the old fish were healthier and even lived longer.
Interestingly, a link was also found between the subunit and human ageing. Significantly lower levels of the particular subunit were measured in samples from elderly patients. In addition, it was possible to show in the human samples that the less frail a person is in old age, the higher the level of this particular kinase subunit.
“Of course, we don’t yet know whether in humans the [subunit] is actually responsible for healthier ageing. In the next step, we will try to find molecules that activate precisely this subunit and investigate whether we can use them to positively influence ageing,” Antebi added.
News
Low doses of weight loss drugs may slow ageing

Microdoses of weight loss drugs like Ozempic could slow ageing and increase longevity, according to new research in mice.
The study found that exenatide, a drug with similar chemical make-up to Ozempic, produced molecular changes in mice that opposed typical patterns seen with ageing across multiple organs.
Scientists treated mice starting at 11 months of age with small doses of the drug for about 30 weeks, then compared tissue samples from brain, liver, kidney, muscle and fat.
Researchers from the Chinese University of Hong Kong measured levels of RNA and DNA modifications, proteins and metabolism-related molecules to assess how age-related molecular signatures had changed in each tissue.
The treated mice showed metabolic health consistent with younger animals, with their molecular “age-signature” significantly shifted to a younger-looking profile compared with untreated older mice.
Many of the drug’s positive effects appeared to involve brain activity, suggesting the brain acted as a hub influencing the ageing profiles of multiple organs throughout the body.
Exenatide and semaglutide (sold as Ozempic and Wegovy) are GLP-1 receptor agonists. These medicines mimic a naturally occurring hormone in the gut and brain that regulates appetite, helping people feel fuller for longer.
Originally developed for diabetes treatment, these drugs have surged in popularity for weight loss. A new trend has emerged online with some people reportedly taking very small doses for longevity, though health experts warn the anti-ageing effect has not been proven in humans.
“Our work has provided multifaceted evidence for a comprehensive body-wide anti-ageing strategy,” the researchers wrote. “Future longitudinal studies are necessary to explore whether GLP-1R agonism may complement other anti-ageing methods.”
The study examined multiple biological markers of ageing, including epigenetic modifications (changes to DNA that affect gene activity without altering the genetic code), protein levels and metabolic indicators across different tissues.
The findings showed consistent changes across many tissues that opposed typical ageing patterns. However, researchers emphasised several important limitations to their work.
The results were observed only in mice, not humans, meaning whether the drug has any real effect on human ageing remains unknown. The study was conducted on middle-aged mice, so the effects might not be the same in very old animals.
Additionally, while the drug appeared to induce many molecular signs of younger age across tissues, the study did not prove that actual biological ageing was reversed or that the mice lived longer.
GLP-1 receptor agonists work by binding to receptors that respond to the GLP-1 hormone. This binding triggers metabolic processes, including insulin release and appetite suppression, and potentially, as this study suggests, molecular changes linked to younger biological age.
The researchers hope their findings will lead to larger clinical trials and help in developing anti-ageing drugs. However, they stress that longitudinal studies tracking subjects over extended periods are necessary to determine whether these drugs could form part of a comprehensive anti-ageing strategy.
The growing interest in using diabetes and weight-loss drugs for longevity reflects wider trends in anti-ageing research, where scientists increasingly examine how existing medicines might have benefits for healthspan and lifespan.
Experts caution that people should not start taking these medicines for anti-ageing purposes based on animal studies alone, as human trials are needed to establish safety and efficacy for this use.
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