Does calorie restriction slow aging? What the CALERIE trial found

Calorie restriction slowed aging on one measure and left the others unchanged. CALERIE is the only long randomised trial of eating less in healthy adults who are neither underweight nor obese: 220 people aged 21 to 50 spent two years either cutting calories or eating as they liked [1][2]. On a blood test called DunedinPACE, which estimates how much biological aging a person accumulates per calendar year, the restriction group aged more slowly than the control group [1]. Other blood estimates of biological age from the same samples, including two named PhenoAge and GrimAge, did not shift, and the researchers describe the effects they did find as small [1].

The trial asked for a 25% cut. People managed about 12%, an average of 2,170 calories a day over two years instead of 2,467, while the comparison group barely changed at all [2]. They lost 7.5 kg on average, roughly 71% of it fat, while the group eating freely gained 0.1 kg [2]. Four out of five people assigned to restriction stayed in the trial to the end [3].

The firmest results were not about aging clocks at all. Over two years, and even after the researchers accounted for the weight people had lost, the restriction group improved on every conventional heart-and-metabolism marker the trial tracked [2]:

• LDL cholesterol, the kind that builds up inside artery walls, and the ratio of total cholesterol to HDL
• both numbers in a blood pressure reading
• C-reactive protein, a blood marker that rises when the body is inflamed
• insulin sensitivity, meaning how readily the body responds to its own insulin

Two later analyses of the same stored samples lean the same way. A cardiometabolic aging score built from twelve routine blood markers advanced about 1.2 years less in the restriction group across the two years, somewhere between roughly 0.6 and 1.8 years less [12]. Blood levels of several markers of cellular senescence - cells that have stopped dividing but stay alive and leak inflammatory signals - fell at both 12 and 24 months compared with eating freely [10].

Not everything moved. Telomeres, the protective caps on the ends of chromosomes that shorten each time a cell divides, showed no overall difference after two years, with the restriction group trending towards faster shortening during the weight-loss year and slower shortening during the maintenance year [4]. The 20 people who regained more than 5% of their starting weight lost the insulin improvements they had made [9].

Eating less did not make people miserable. Against the control group, the restriction group reported slightly better mood, less tension, better general health and, at 12 months, longer sleep, and no measure of quality of life got worse [15]. The gaps were narrow: on a 63-point depression questionnaire it came to under one point [15].

The trial was built around measurements of how the body uses energy, and those moved. Triiodothyronine, or T3, the thyroid hormone that sets how fast cells burn energy, fell further in the restriction group at both 12 and 24 months, and tumour necrosis factor alpha, a protein cells use to signal inflammation, fell more by 24 months [3]. Energy burned at rest, adjusted for the weight people lost, also dropped more under restriction during the first year [3].

The nutrient-sensing side matters more for aging. Insulin and insulin-like growth factor 1, or IGF-1, a growth signal that rises and falls with how much a person eats, make up what researchers call a nutrient-sensing pathway: the body's running read on how much energy is coming in [9]. In CALERIE, people who kept the weight off held on to lower insulin responses and a shifted IGF-1 signal, and those who regained the weight lost both [9].

Fewer senescent cells may be part of the same process. Senescent cells build up with age and secrete inflammatory molecules; in CALERIE the drop in blood markers of senescence tracked with the improvement in insulin sensitivity, and fat tissue from a subset of participants showed lower activity in senescence-related genes after restriction [10].

CALERIE tested roughly a 12% cut, not the 25% it aimed for, so it is evidence about moderate restriction rather than the deep restriction fed to animals in laboratory studies [2]. It ran for two years and measured markers in blood, not illness or death: the researchers who found the slower pace of aging say plainly that a real test of the idea needs trials long enough to count chronic diseases [1].

Which test you use changes the answer. The pace-of-aging measure moved; PhenoAge and GrimAge, two other blood estimates of biological age, did not, and the shift in the one that moved was small [1]. Telomere results were inconsistent enough that the authors could not say whether restriction helped, hurt, or did nothing [4]. Several supporting results - the senescence markers, the cardiometabolic aging score, the weight-regain comparison - come from later analyses of stored samples rather than questions the trial was built to answer [9][10][12].

The people studied were a narrow slice:

• adults aged 21 to 50, average age 38, so nothing here speaks to people in their seventies, the group most aging research is aimed at [15]
• a starting body mass index between 22.0 and 28.0, which rules out anyone underweight and anyone with obesity [15]
• women who had not reached menopause [4], and about seven in ten participants were women [15]
• volunteers who signed up at three US research centres [2]

A typical participant was a 38-year-old woman with a body mass index of 25, asked to cut a quarter of her calories and managing closer to an eighth: about 300 fewer calories a day than she had been eating [2][15]. That went on for two years under measurement at a research centre, and even so, around one in five people in the restriction group did not finish [3].

A secondary analysis suggests the how mattered alongside the how much. People whose first meal of the day landed at a similar time each day lost more weight than people whose breakfast time wandered, and the size of the calorie cut itself explained about 41% of why some people lost more than others [13]. The trial never shortened anyone's eating window - restriction and control groups ate across the same span of hours - so CALERIE says nothing about time-restricted eating [13].