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Fasting interventions become less effective with age, study finds

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Killifish age in fast motion. The bright colours of their youth fade after just a few months.

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.

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Low doses of weight loss drugs may slow ageing

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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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Eating cheese linked to lower dementia risk

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Cheese eaten at least weekly was linked with a lower dementia risk in a study of nearly 8,000 older adults.

Tracking 7,914 people aged 65 or over for three years, the study found a dementia rate of 3.4 per cent among weekly cheese eaters, compared with 4.5 per cent in those who avoided cheese.

That equals about 10 to 11 fewer cases per 1,000 people, suggesting a modest effect at population level.

Researchers at Niimi University in Japan analysed participants split into two groups: about half ate cheese at least once a week, while the rest did not.

The study, commissioned by Japanese food company Meiji Co., adjusted for age, sex, education and income.

Seungwon Jeong, a geriatrics researcher at Niimi University, and colleagues, said: “These findings are consistent with prior observational evidence linking dairy intake to cognitive health.

“Although the effect for each person is modest, at a population scale, especially in countries with low cheese intake, such differences could contribute meaningfully to dementia prevention strategies.”

The association held, though weaker, even after accounting for overall diet quality.

People who avoided cheese tended to have less healthy diets, but the link persisted, suggesting cheese itself might confer specific benefits.

Cheese contains nutrients that may support brain health, including vitamin K, which is involved in processes that help maintain cognitive function.

It is also rich in beneficial bacteria that support gut health, and previous research has linked the gut microbiome to brain function.

Fermented dairy products like cheese have been shown to benefit cardiovascular health, which is closely tied to dementia risk because poor heart health can limit blood flow to the brain.

The researchers noted: “Although the present study did not include biomarker or mechanistic assessments, several nutritional characteristics of cheese may provide a plausible explanation for the observed association.”

Biomarkers are measurable biological signals, and mechanistic assessments explore how an effect works.

The findings add to evidence that lifestyle factors, including exercise, diet, social engagement and cognitive activities, may influence dementia risk.

While the study shows association rather than causation, it indicates that dietary choices could play a role in brain health.

Dementia affects at least 50 million people worldwide, a number expected to rise as populations age.

The United Nations has declared it a public health priority, particularly in countries such as Japan where demographic shifts are creating an increasingly elderly population.

The researchers emphasised that the statistics are not strong enough to guarantee cheese will prevent dementia, but the indications suggest it could form part of a brain-healthy diet.

The researchers concluded: “Further research is warranted to clarify dose-response relationships, cheese subtypes, and underlying mechanisms.”

The study controlled for multiple variables but could not eliminate all confounding.

People who regularly eat cheese may have other lifestyle characteristics that protect against dementia, though the team attempted to account for known influences.

Japan has traditionally low cheese consumption compared with Western countries, making it an informative population for studying potential health impacts of dairy products.

The findings may be especially relevant where cheese intake is minimal but dementia rates are rising.

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Discovery could change how people manage diabetes

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Metformin, a cheap century-old drug, cut insulin use by 12 per cent in adults with type 1 diabetes, a recent Australian study has found.

A randomised trial in 40 adults with long-term type 1 diabetes found insulin doses were 12 per cent lower with metformin over six months, with no change in blood sugar control.

The team had expected metformin to improve insulin resistance, as in type 2 diabetes, but instead saw lower insulin needs without changes in insulin resistance.

Researchers at the Garvan Institute of Medical Research, who describe this as the first randomised controlled trial of its kind, ran the six-month study.

Dr Jennifer Snaith, study co-leader at Garvan, said: “Insulin resistance is a growing problem in type 1 diabetes.

“Not only does it make regulating blood sugar levels difficult, but it is an underappreciated risk factor for heart disease, which is one of the biggest causes of health complications and deaths in those with type 1 diabetes.”

The researchers randomised 40 adults with long-term type 1 diabetes to take either metformin or a placebo for six months.

They examined whether their insulin resistance changed over that time through a sophisticated and comprehensive research technique, called a clamp study, that allowed the team to map insulin resistance in different parts of the body.

A clamp study is a precise test that measures how well the body responds to insulin by controlling blood sugar and insulin levels while monitoring glucose uptake in different tissues.

Dr Snaith said: “Although we didn’t find changes to insulin resistance from the use of metformin, we did show that people taking it used around 12 per cent less insulin than those on placebo.

“This is an important result.

“Insulin is a relatively old treatment which, while lifesaving, comes with significant mental and physical burden.

“This means that lowering the amount of insulin used is a priority for many people living with type 1 diabetes. We have shown that a very cheap, accessible medication may serve this purpose and this is very exciting.”

The team is now investigating how metformin reduces insulin needs in type 1 diabetes.

If confirmed, this could mean fewer injections, lower costs and a lower risk of hypoglycaemia, and may also help limit weight gain linked to high insulin doses.

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