Can restricting calories slow biological aging and help healthy adults live longer? A first-of-its-kind trial in humans suggests that it might.
The landmark study, published on February 9 in the journal Nature Aging, found that a two-year intervention that required participants to cut 25 percent of their daily calories slowed the pace of aging by 2 to 3 percent. This translates to a 10 to 15 percent reduction in mortality risk, the researchers say — about the same level of risk reduction as quitting smoking.
“Our findings are important because they provide evidence from a randomized trial that slowing human aging may be possible,” said Calen Ryan, PhD, a research scientist at Columbia University’s Butler Aging Center in New York City and co-lead author of the study, in an email.
Although many people might find this level of caloric restriction too difficult, the study supports the concept that behavioral changes — without any drugs — can have a measurable impact on the pace of aging, Dr. Ryan said.
“This paves the way for future studies of other interventions, such as time-restricted eating or intermittent fasting, which might be more scalable and achievable in a broader sector of the population,” said Ryan.
Calorie Restriction Has Benefits for Metabolism and Heart Health
The current study is part of an ongoing investigation called CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) that began in 2006.
Previous studies using CALERIE trial data have shown multiple benefits from cutting calories. One investigation found that calorie restriction slowed aging-related changes in physiology related to the liver, kidneys, metabolism, blood vessels, and the immune system. Another study showed that calorie restriction reduced risk factors for heart disease and type 2 diabetes and improved cardiovascular and metabolic health.
The new study was designed to explore those earlier findings. “We wanted to find out if signs of slowed aging at the organ-system level were also apparent at the cellular level,” says Daniel Belsky, PhD, associate professor of epidemiology at Columbia Mailman School of Public Health and a scientist at the Butler Aging Center in New York City.
How Do You Measure Biological Age?
Decades of research using animal models have demonstrated that caloric restriction (without malnutrition) enhances the life span and so-called health span. But does this hold true for humans?
“Given how long humans live, it’s not feasible to do a rigorous clinical trial to answer this question,” says study coauthor Daniel Parker, MD, geriatrician and assistant professor of medicine and neurology at Duke Health in Durham, North Carolina.
Instead, researchers have devoted serious efforts to determine how to measure a person’s “biological age,” as opposed to their chronological age, to find signs of slowed aging, says Dr. Parker. One promising approach to measuring biological age, he says, is to analyze what’s called the epigenome.
“While our genetic code remains largely unchanged over the course of our lives, our cells are constantly making reversible modifications to our DNA that turn genes on and off. These reversible modifications to our DNA are referred to as the epigenome,” he explains.
Researchers can compare these epigenetic changes to a reference population from earlier research to estimate a person’s biological age, says Parker.
Study Participants Were Closely Monitored to Make Sure They Were Getting Necessary Nutrients
In the most recent CALERIE study, researchers randomly assigned 220 participants to the calorie restriction group or a control group that had no restrictions on their food intake. The calorie restriction group consisted of 143 people (44 men and 99 women), while the control group consisted of 75 people (22 men and 53 women).
The study population was 76 percent white, 15 percent African American, and 9 percent Asian, Native American, or Pacific Islander, with an average age of 38. The participants’ average baseline body mass index (BMI) was 25.1, which would place participants in the normal and overweight weight range, per the National Heart, Lung, and Blood Institute.
Scientists used sophisticated techniques to estimate how many calories each person needed to maintain their body weight. Then they took that baseline and set individual goals that shaved 25 percent from that number — so if a person’s baseline was 2,000 calories a day, they were supposed to consume 1,500 calories.
That target level of 25 percent was selected because this degree of calorie restriction has had the best results in improving life span and health span in animal models and was found to be feasible in most participants in the original pilot study from 2006, according to the authors.
“It’s important to note that this was a study of moderate caloric restriction without malnutrition,” says Parker. Individuals who were underweight, depressed, or had a history of diabetes, heart disease, or an eating disorder were not enrolled in the study, he says.
Everyone in the study was advised about how to cut calories and still get the recommended nutrients, and they were given options for eating patterns that would accommodate their cultural and individual preferences.
“Participants in this study were closely monitored throughout the study to make sure they were meeting all their macronutrient requirements, and participants’ weight was closely monitored. If anyone lost too much weight, they were instructed to increase their caloric intake,” Parker says.
Maintaining a 25 percent calorie reduction proved challenging — the majority fell short of the goal, and the average calorie reduction was 12 percent by the end of the trial. However, study participants still lost an average of 16 pounds over the course of the two-year study.
“Reassuringly, there was no evidence that caloric restrictions negatively affected participants’ sleep, cognitive performance, or quality of life,” says Parker.
Fewer Calories Resulted in Slower Aging
To measure the impact of calorie restriction on biological aging, investigators analyzed blood samples collected from trial participants at pre-intervention baseline and after 12 and 24 months of follow-up.
They found that calorie restriction slowed the pace of biological aging over time. Additionally, there appeared to be a dose-response effect: Participants who reduced their caloric intake to a greater extent had a greater decline in their pace of biological aging, says Parker. “These findings are exciting because they provide evidence that the pace of biological aging isn’t set in stone, but can be affected by interventions like caloric restriction,” he says.
These findings add to what is currently known about calorie intake and biological aging, says Jamie Justice, PhD, researcher and assistant professor of gerontology and geriatric medicine at Wake Forest School of Medicine in Winston Salem, North Carolina. Dr. Justice was not involved in the CALERIE study.
Because eating less leads to weight loss (which can have many health benefits), more research is needed to strengthen the findings on how calorie restriction directly impacts aging, she says.
A follow-up of trial participants is now ongoing to determine if the intervention had long-term effects on healthy aging.
Why Would Eating Fewer Calories Slow Down Aging?
In simple terms, the current thinking is that calorie restriction affects nutrient-sensing pathways and energy metabolism in ways that reverse or reduce the effects of aging, says Dr. Belsky. These pathways are called “nutrient-sensing” because nutrient levels influence their activity.
Part of that effect is due to a process called hormesis, says Justice. “When you give the body or an organism a little bit of a stressor, over time it can activate certain pathways that can actually end up promoting health,” she says.
Take exercise as an example, says Justice. “You’re stressing the body just a little bit and by doing that, some of these key pathways have to change how they function and signal. In a similar fashion, restricting calories also gives your body a little bit of stress at the cellular level and creates changes in pathways that are associated with lifespan, including those that involve human growth hormone and insulin,” she says.
Intermittent Fasting or Time-Restricted Eating May Induce Similar Benefits
If caloric restriction isn’t for you, take heart — there’s growing evidence that other methods may “trick” the body and achieve similar benefits, says Justice.
Although the data is mixed on intermittent fasting as far as its effectiveness in reducing calorie intake, Justice says, “Time restricted eating seems to have really profound effects, especially in people who are in their forties and fifties, who want to either lose a little weight or who are at a healthy weight and just looking to improve their biology.”
Is It Safe to Restrict Calories Over Months or Years?
Before adopting any sort of calorie-restrictive diet, talk with your doctor, says Justice. “It needs to be done under the care and guidance of a professional because it’s not without risks,” she says.
As long as a person is getting the recommended amount of nutrients, restricting calories is generally safe, unless they are already underweight or can become underweight due to the caloric restriction, says Julia Zumpano, RD, with Cleveland Clinic’s Center for Human Nutrition.
Ideally, a person should first meet with a registered dietitian to help them create a plan and make sure they are meeting all nutrient needs, she says.
“I would advise restricting calories from foods and beverages that provide empty calories (very little to no nutrients). Examples include soda, sweetened coffee drinks, punch, lemonade, candy, pastries and cookies, fast foods, chips, sour cream, creamy salad dressings, and cream cheese,” says Zumpano.