Intermittent Fasting vs. Calorie Restriction—What’s Better?

Does the secret to living a longer, healthier life lie in skipping meals or eating smarter? A groundbreaking study has finally weighed in on the debate between calorie restriction and intermittent fasting for longevity. The results may surprise you…

Key Takeaways

• Calorie restriction outperforms intermittent fasting for longevity, with mice on a 60% reduced-calorie diet living 36% longer than those on unrestricted diets.
• Genetic resilience plays a key role in lifespan; mice maintaining weight and immune health under caloric restriction lived the longest.
• Weight loss may not equate to longevity, as losing weight during calorie restriction was associated with shorter lifespans, challenging traditional views on metabolic health markers.

What We Know About Calories and Longevity

The research shows that an animal that eats less food or eats less often will live healthier and longer lives. There is also research showing that calorie restriction improves the longevity of people, too. But it’s unclear whether calorie restriction or intermittent fasting is best if you want to live longer.

Now, in one of the most important longevity studies to date, researchers found calorie restriction was superior. However, the picture is not so clear, because—wait for it-- diet turns out not to be the key factor in longevity at all.

For almost a century, laboratory studies consistently demonstrated that calorie restriction (CR) extends lifespan in various species. But let’s face it, few of us always want to be hungry! That’s simply no way to live.

Unsurprisingly, scientists turned to studying more tolerable approaches to dietary restriction. Fortunately, these still show health and lifespan benefits in animal research on both time-restricted feeding (calorie restriction) and intermittent fasting (IF). The former limits daily intake to a four to 12-hour window, while the latter restricts food to one or several days a week.

In rodent studies, intermittent fasting extends life and protects against obesity, cardiovascular disease, hypertension, diabetes, and neurodegenerative diseases. These benefits can occur even without an overall reduction in calories.

That said, there’s still limited data on the differences between calorie restriction and intermittent fasting regarding healthy aging and longevity, and responses to these diets vary between individuals.

In mice and non-human primates, the effect is influenced by gender, body size, body composition, and genetics. Meanwhile, human studies have been short term and focused on changes in body weight, fat tissue, energy metabolism, and cardiometabolic risk factors.

Limited knowledge makes it hard to predict how individuals will respond to dietary restrictions, so if specific biological predictors could be found, they would help tailor the diet to individual needs.

To this end, scientists at The Jackson Laboratory in Maine carried out an extensive and pivotal experiment in mice.

Severe Calorie Restriction Extends Life Most

They used 960 female mice, with each mouse being genetically distinct to better represent the genetic diversity of the human population. Researchers assigned each one to any of the following five diets:

• Unrestricted – eat as much as they want
• Calorie restriction – 60% of their usual intake each day
• Calorie restriction – 80% of their usual intake each day
• Intermittent fasting – fasted on one day a week, unrestricted on other days
• Intermittent fasting – fasted on two consecutive days, unrestricted on other days

Next, they studied the mice for the rest of their lives with periodic blood tests and extensive overall health evaluation. This is how long each group lived on average:

• Unrestricted - 25 months
• Intermittent fasting - 28 months (both fasting regimens outlined above combined)
• Calorie restriction 80% - 30 months
• Calorie restriction 60% - 34 months

The clear winner was the group that ate the least. The nine-month difference between this group and those that could feed on as much chow as they liked is considerable in a species that lives less than three years.

Read more about the health benefits of intermittent fasting here.

There was also another interesting finding.

The Importance of Resilience

Diets extremely low in calories extended lifespan regardless of body fat and glucose levels — both typically seen and focused on as markers of metabolic health and aging in human studies.

What’s more, the mice that lived the longest lost the least weight despite eating less. They maintained their body weight, body fat percentage, and immune cell health while those that lost the most weight tended to have low energy, compromised immune and reproductive systems, not to mention shorter lives.

Gary Churchill, senior author of the study, published in the journal Nature in October, tells us why: “Our study really points to the importance of resilience. The most robust animals keep their weight on even in the face of stress and caloric restriction, and they are the ones that live the longest.”

Good news, right? Sort of…

Genetics Played a Key Role

If you look more closely at the research, mice eating the fewest calories had lifespans ranging from a few months to four and a half years. How could this be? Scientists chalked up this wide variation in lifespan within each group to genetic factors. For instance, genetic factors had a far greater impact on lifespan than diets, highlighting how underlying genetic features, yet to be identified, play a major role in how such diets affect future health.

Sadly, this study suggests you need to win the genetics jackpot to reach the century mark, as summed up by Professor Churchill. “If you want to live a long time…what you want is a very old grandmother.”

But, take heart: other studies have suggested that your diet and lifestyle can supersede your genetic code when it comes to health and longevity. What’s more, it also appears that human aging researchers are looking in the wrong place.

Cut Calories Not Weight

Factors influencing metabolism such as weight, body fat percentage, body temperature, and blood glucose levels, are traditionally put forward to explain why certain diets extend life. But the Jackson Lab findings cast doubt on this. Instead, immune system health and traits related to red blood cells were more clearly connected to lifespan.

“While caloric restriction is generally good for lifespan, our data show that losing weight on caloric restriction is actually bad for lifespan,” Professor Churchill explained. “So, when we look at human trials of longevity drugs and see that people are losing weight and have better metabolic profiles, it turns out that might not be a good marker of their future lifespan at all.”

These findings don’t mean diet isn’t important, as Professor Churchill emphasizes:

“If you want to live a long time, there are things you can control within your lifetime such as diet. A more moderate level of calorie restriction might be the way to balance long-term health and lifespan.”

Summary

A landmark study from The Jackson Laboratory compared the effects of calorie restriction (CR) and intermittent fasting (IF) on longevity using genetically diverse mice. Results showed that mice on severe calorie restriction lived significantly longer than those on intermittent fasting or unrestricted diets, with a 60% calorie reduction extending lifespan by 36%. Interestingly, the study revealed that resilience to calorie restriction—maintaining weight and immune health—played a greater role in longevity than weight loss or metabolic markers. Ultimately, genetics emerged as the most critical factor influencing lifespan, challenging traditional beliefs about aging and diet.

Frequently Asked Questions

What is calorie restriction (CR)?

Calorie restriction involves reducing daily caloric intake, often by 20–40%, while maintaining essential nutrient intake.

What is intermittent fasting (IF)?

Intermittent fasting alternates periods of eating and fasting, such as time-restricted feeding or fasting on certain days of the week.

Why does calorie restriction work better than intermittent fasting?

The study suggests that calorie restriction more consistently supports longevity by enhancing resilience and immune health, rather than focusing on weight loss or metabolic markers.

Does intermittent fasting still have benefits?

Yes, intermittent fasting can improve metabolic health and reduce risks for obesity, diabetes, and cardiovascular diseases, even without significant calorie reduction.

Is genetics more important than diet for longevity?

According to the study, genetics plays a significant role in determining how diets affect lifespan, making it a critical factor alongside diet and lifestyle.