Research
Calorie restriction stimulates healthy ageing genes, study finds

A new study sheds light on the link between calorie intake and healthy ageing in humans.
Reducing overall calorie intake has long been known to delay the progression of age-related diseases in animal models. A new study, led by researchers at the National Institutes of Health, suggests the same biological mechanisms may also apply to humans.
Calorie restriction, which involves decreasing calories without depriving the body of essential vitamins and minerals, may rejuvenate muscles and activate biological pathways important for good health, according to the study published in Aging Cell.
Researchers analysed data from participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), a study supported by the National Institute on Aging (NIA) that examined whether moderate calorie restriction conveys the same health benefits seen in animal studies.
During a two-year span, the goal for participants was to reduce their daily caloric intake by 25 per cent, but the highest the group was able to reach was a 12 per cent reduction. Even so, this slight reduction in calories was enough to activate most of the biological pathways that are important in healthy ageing.
“A 12 per cent reduction in calorie intake is very modest,” said study author and NIA scientific director Luigi Ferrucci, M.D., PhD. “This kind of small reduction in calorie intake is doable and may make a big difference in your health.”
The research team next sought to understand the molecular underpinnings of the benefits seen in limited, previous research on calorie restriction in humans.
One study showed that individuals on calorie restriction lost muscle mass and an average of 20 pounds of weight over the first year and maintained their weight for the second year. However, despite losing muscle mass, calorie restriction participants did not lose muscle strength, indicating calorie restriction improved the amount of force generated by each unit of muscle mass, called muscle-specific force.
For the current study, scientists used thigh muscle biopsies from CALERIE participants that were collected when individuals joined the study and at one-year and two-year follow-ups.
To figure out which human genes were impacted during calorie restriction, the scientists isolated messenger RNA (mRNA), a molecule that contains the code for proteins, from muscle samples.
The team determined the protein sequence of each mRNA and used the information to identify which genes originated specific mRNAs. Further analysis helped the scientists establish which genes during calorie restriction were upregulated, meaning the cells made more mRNA; and which were downregulated, meaning the cells produced less mRNA.
The researchers confirmed calorie restriction affected the same gene pathways in humans as in mice and non-human primates. For example, a lower caloric intake upregulated genes responsible for energy generation and metabolism and downregulated inflammatory genes leading to lower inflammation.
“Since inflammation and ageing are strongly coupled, calorie restriction represents a powerful approach to preventing the pro-inflammatory state that is developed by many older people,” said Ferrucci.
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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