Caloric restriction: longevity, not deprivation

People often ask me about the difference between intermittent fasting, time-restricted eating and caloric restriction. Caloric restriction (CR) is not a fad or a short-term diet—it's the long-term practice of reducing daily calorie intake by around 20–30% (sometimes up to 50%) below habitual levels, without depriving the body of essential nutrients. Unlike fasting or time-restricted eating, which focus on when you eat, caloric restriction is about how much you eat consistently over time.

What happens when we eat less?

Scientists have known for nearly a century that eating less can extend life in animals. In fact, a 1935 study found that rats fed a nutritious but calorie-restricted diet lived longer than their free-feeding peers. Since then, the same effect has been shown across an astonishing range of species—from yeast to monkeys.

Caloric restriction delays the onset of age-related diseases and enhances metabolic function. It’s still the only non-genetic intervention consistently shown to extend lifespan across multiple organisms.

Rhesus monkeys and the lessons for humans

Two landmark studies at the University of Wisconsin (UW) and the National Institute of Aging (NIA) looked at the effects of caloric restriction in rhesus monkeys—an important model due to their genetic similarity to humans.

Both studies found fewer age-related diseases and better glucose control in calorie-restricted monkeys. However, only the UW study found a significant survival benefit: calorie-restricted monkeys lived longer than controls. The NIA study, on the other hand, found no difference in overall survival.

So why the mixed results? The monkeys’ genetics, the makeup of their diets, and even their feeding schedules differed. For example, the UW monkeys ate a higher-sugar diet and were only fed during the day, while the NIA monkeys ate a more natural, seasonal diet and had food available overnight. These differences remind us that how we implement caloric restriction matters—and might interact with other lifestyle or dietary factors.

A closer look at humans

In humans, short-term studies show promising metabolic effects. Just three weeks of 20% caloric restriction can reduce resting metabolic rate, lower blood pressure, and improve glucose levels. Longer trials (such as a 10-week study) show even greater reductions in energy expenditure, inflammation, and blood pressure.

But what happens if you stick with it?

In a study of people who had voluntarily practiced long-term caloric restriction (30% below their usual intake for 3–15 years), researchers observed reduced inflammation, better autophagy (the body’s cellular recycling system), and healthier hormone profiles compared to people eating a standard Western diet.

The CALERIE trials—specifically designed to study caloric restriction in humans—offer even more insight. In the CALERIE 2 study, 218 normal-weight or slightly overweight adults aimed for a 25% calorie reduction for two years. Although most achieved only 12% on average, they still experienced significant improvements in cholesterol, triglycerides, blood pressure, inflammation, and insulin sensitivity.

So, even moderate calorie reduction over time seems to have real metabolic benefits.

How does it work?

Caloric restriction seems to turn on ancient survival mechanisms. At the molecular level, it lowers activity in pathways like IGF-1 and mTOR (both linked to aging and cancer risk), while enhancing protective responses like autophagy, DNA repair, and stem cell maintenance.

Some key players include:

• Sirtuins – enzymes that promote DNA repair and longevity.

• FOXO proteins – which regulate stress resistance and metabolism.

• AMPK and Nrf2 – central to energy balance and antioxidant defense.

Together, these pathways help the body shift from a “growth” mode to a “maintenance and repair” mode.

But is it sustainable?

That’s the big question. While CR has clear biological benefits, very few people manage to stick with it long term. Even in clinical trials, participants rarely reach the full level of restriction and often gradually increase intake over time.

There’s also the issue of protein: calorie-restricted humans often compensate by eating more protein for satiety, which can activate pathways like mTOR and IGF-1—potentially blunting some of the longevity effects seen in low-protein CR diets in animals.

Alternatives that might be more realistic

Thankfully, CR isn’t the only route to these benefits. Other, more flexible approaches seem to activate similar cellular and metabolic pathways:

• Time-restricted eating – eating all meals within a daily window (e.g., 8 hours).

• Alternate-day fasting – eating normally every other day, and restricting intake in between.

• Prolonged fasting – fasting for multiple days at regular intervals.

These strategies induce an “energy crisis” at the cellular level—prompting fat burning, ketone production, and improved insulin sensitivity. Crucially, they appear to preserve lean muscle mass while improving metabolic flexibility, which may be even more protective in humans than calorie restriction alone.

The bottom line

Caloric restriction has remarkable effects in animals and shows promise in humans—but it’s not easy or always sustainable. Still, the research is clear: regularly reducing caloric load, especially from ultra-processed foods and excess carbohydrates, lowers inflammation, improves metabolism, and may slow the processes of aging and chronic disease.

If a long-term 30% reduction isn’t realistic for you, don't worry—other practices like intermittent fasting or time-restricted eating may offer similar benefits, and might be easier to stick with in real life.