Can nutrients in our foods mimic calorie restriction and increase our healthspan?
Scroll through social media and you will soon encounter advice about living longer, from fasting plans and supplements to elaborate daily routines. Yet reaching an advanced age tells us little about how healthy or independent those later years will be.
Researchers often use the term healthspan for the years spent in good health, free from disability or chronic disease. In 2021, global life expectancy was 71.4 years, while healthy life expectancy was 61.9 years, according to the World Health Organization (WHO). That represents a gap of nine and a half years. A separate analysis estimated that this gap widened in 203 of 204 countries and territories between 1990 and 2023.
The WHO takes a broader view of healthy ageing, focusing on the abilities that allow people to do what they value, such as undertaking daily tasks, maintaining relationships and contributing to society. This recognises that people can live well while managing a health condition. “Functional healthspan” describes how long someone maintains the capacities needed for independent living.
As we age, declining muscle strength and mass, reduced aerobic fitness and even “inflammaging” (or low-grade inflammation) become more prevalent. These changes vary considerably between people. Diet, physical activity and sleep can influence how well we age, although income, housing, healthcare and the wider environment also play important roles.
Why researchers study calorie restriction
One intensively studied approach to ageing is calorie restriction: reducing energy intake by about 20–40% while still obtaining enough essential nutrients.
Calorie restriction can extend lifespan in organisms ranging from yeast to rodents, although its effects vary with species, genetics, sex, age and diet. Evidence in humans is less certain.
The largest long-term human trial of calorie restriction, the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE), followed 218 healthy adults without obesity for two years. Participants assigned to calorie restriction reduced their intake by 12% on average. They experienced improvements in measures linked with cardiovascular and metabolic health, including blood pressure, insulin sensitivity and blood markers of inflammation. They also lost about 5.4kg of body fat and 2kg of lean mass, while bone mineral density fell slightly at the spine and hip.
Although the trial examined age-related biomarkers, it did not establish whether calorie restriction improves functional healthspan or extends human life. Sustaining even this degree of restriction can be difficult.
Researchers are also studying compounds that affect similar cellular processes that impact ageing without requiring people to eat substantially less. These are known as calorie-restriction mimetics (CRMs), and many are found in our foods.
CRMs may reduce signals associated with cell growth, encourage autophagy, through which cells recycle damaged components, or influence how cells sense energy, function metabolically and support mitochondria to produce energy. Much of this evidence comes from cells and animals, however, and influencing one cellular mechanism does not necessarily improve health or lifespan.
What have human studies found?
One CRM, spermidine, is a compound found in wheat germ, mushrooms, legumes and nuts. In an observational study of 23,894 US adults, higher estimated spermidine intake was associated with a lower risk of death during follow-up, both overall and from cardiovascular disease. However, this does not establish cause and effect. People who eat more spermidine-rich foods may have healthier diets overall, or differ in other ways that could help explain the findings.
A small three-month pilot trial involving 30 older adults initially suggested that spermidine might improve memory. However, a larger 12-month randomised trial involving 100 older adults with subjective cognitive decline found that a spermidine-rich supplement did not improve the trial’s main measure of memory compared with a placebo.
Other compounds proposed as calorie-restriction mimetics because they may produce some of the same cellular effects include resveratrol, found in grapes and berries; catechins, found in green tea and cocoa; and quercetin, found in onions and apples. In a study of 30 adults aged 65–80, resveratrol supplementation combined with exercise improved measures of muscle strength, power and resistance to fatigue. Older adults taking quercetin during six weeks of resistance training produced more force with their knee muscles, but did not improve physical tasks such as rising from a chair.
Although these studies highlight some healthspan benefits, both tested supplements (not wholefoods), and neither assessed whether proposed calorie-restriction mechanisms caused the changes.
Another possible CRM, urolithin A, is produced by our gut bacteria when they break down substances called ellagitannins found in foods including pomegranates and walnuts. In a trial of 66 adults aged 65–90, urolithin A supplementation improved muscle endurance and measures of mitochondrial health, but did not significantly improve the study’s main outcomes: six-minute walking distance and the muscles’ capacity to produce energy.
A separate industry-sponsored trial in middle-aged adults reported urolithin A improved muscle strength, aerobic fitness and walking speed, but not peak muscle power. These results highlight functional benefits, but do not show that eating pomegranates or walnuts will produce the same effects, or that urolithin A can directly extend healthspan.
What should people do now?
Research into these compounds may help scientists understand how cells respond to nutrients and ageing. Current findings do not justify trying to obtain large doses of individual compounds, particularly from supplements.
More reliable evidence concerns overall habits. A 2025 study that followed more than 105,000 adults for up to 30 years found that several healthy dietary patterns were associated with reaching older age free from major chronic disease and with good cognitive, physical and mental health. These diets generally included plenty of fruit, vegetables, whole grains, nuts, legumes and unsaturated fats (such as omega-3s). Sufficient high-quality protein is also important for maintaining muscle, particularly in combination with resistance exercise.
Physical activity remains central to preserving function. UK guidance recommends that older adults undertake activities that improve strength, balance and flexibility on at least two days each week, alongside regular aerobic activity.
Foods containing proposed calorie-restriction mimetics can form part of a varied, nourishing diet. Mediterranean diets typically emphasise vegetables, fruit, legumes, whole grains, nuts and olive oil. Traditional Okinawan diets have centred on sweet potatoes and other vegetables, alongside soy foods and small amounts of fish. Both have been associated with healthy ageing, although these associations do not show that individual CRM compounds are responsible for their benefits.
Research in humans has yet to show that these compounds reproduce the effects of calorie restriction or extend healthspan. For now, the strongest evidence for ageing well supports a varied, nutritious diet and purposeful physical activity, while the benefits of CRM nutrients continues to gather scientific interest.