Biology of aging: why curbing calories counts

Posted by Joe Brady on September 25, 2022September 25, 2022

For decades, researchers have studied eating patterns—what, when, and how much we eat—to see how they might help us avoid age-related diseases like heart disease, diabetes, and dementia. They are also interested in learning more about how different eating patterns might affect the health of our musculoskeletal system, which comprises the body’s muscles, bones, and connective tissue.

Of particular interest to researchers is calorie restriction, or more properly termed a nutrient-dense diet which involves reducing average daily caloric intake below what is typical or habitual while increasing nutrition to avoid malnutrition or deprivation of essential nutrients. Calorie restriction can be also accomplished by not eating at all for a period of hours or days (known as “intermittent fasting”) or by eating less at some or all meals. Some studies in animals and humans have shown that calorie restriction can lead to improvements in a variety of health conditions. It also extends lifespan for many animal species, though there’s no evidence to confirm lifespan itself increases in people, eating a nutrient-dense diet has been shown to help us avoid many age-related diseases.

What’s the Evidence from Animal Studies?

More animal research has been done on calorie restriction than on fasting. In some experiments, calorie restriction is also a form of fasting because the lab animals consume all their daily allotted food within hours and go many more hours without any food.

In these studies, when rodents and other animals were given 10 percent to 40 percent fewer calories than usual but provided with all necessary nutrients, many showed extension of lifespan and reduced rates of several diseases, especially cancers. But, some studies did not show this benefit, and in some mouse strains, calorie restriction shortened lifespan rather than extending it.

In the worm C. elegans, a fasting diet increased lifespan by 40 percent. A study with fruit flies found that calorie restriction—but not intermittent fasting—was associated with living longer. One study of male mice found that lifelong alternate-day fasting increased longevity, mainly by delaying cancer occurrence rather than slowing other aging processes.

The NIH’s National Institute on Aging (NIA) broadly invests in research to find ways to help people live longer and healthier. As people age, they are more likely to have multiple chronic diseases, and NIA-supported research studies reflect a strong focus on geroscience. This advancing area of science seeks to understand the mechanisms that make aging a major risk factor and driver of common chronic conditions and diseases of older people.

Two National Institute on Aging (NIA)-supported studies in rhesus monkeys sought to find out whether the benefits of calorie restriction are seen in longer-lived species. In both studies, the monkeys were kept on a calorie-restriction diet (30 percent fewer calories than for monkeys in the control groups) for more than 20 years. Although there were differences between the two studies—including monkey breed and type of food—both provided evidence that calorie restriction reduced the incidence of age-related conditions, such as cancer, heart disease, and diabetes. One study found an extension of lifespan, while the other did not. Many of the monkeys are still alive, so the full impact of calorie restriction on their maximum lifespan has yet to be determined.

More than 85 years ago, researchers at Cornell University, Ithaca, New York, observed that some lab rodents lived longer when fed a lower calorie diet that otherwise had the appropriate nutrients1. Since then, many scientists have studied calorie restriction to shed light on the various biological mechanisms that may explain its benefits and perhaps discover a way to extend healthy years of life, known as our healthspan.

Although there have been many studies of calorie restriction since the Cornell findings, the NIA-supported clinical trial CALERIE, which stands for Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy, provided critical data on the impact of this intervention in people. Completed in 2012, CALERIE was the first carefully controlled study to test whether study participants undergoing moderate calorie restriction would display any of the benefits observed in animal studies.

Scientists are working to discover what it is about calorie restriction that may help animals and humans stay healthy as we age. Someday, this research could lead to the development of calorie restriction mimetics—medicines that mimic calorie restriction’s effects to slow the aging process.

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1 McCay CM, et al. The effect of retarded growth upon the length of life span and upon the ultimate body size. Journal of Nutrition. 1935;10(1): 63–79. doi: 10.1093/jn/10.1.63.

2 Ravussin E, et al. A 2-year randomized controlled trial of human caloric restriction: Feasibility and effects on predictors of health span and longevity. Journals of Gerontology, Series A: Biological Science and Medical Science. 2015;70(9):1097-104. doi: 10.1093/gerona/glv057.

3 Spadaro O, et al. Caloric restriction in humans reveals immunometabolic regulators of health span. Science. 2022;375(6581):671-677. doi: 10.1126/science.abg7292.

4 Rhoads TW and Anderson RM. Caloric restriction has a new player. Science. 2022;375(6581):620-621. doi: 10.1126/science.abn6576.

Links:

Calorie restriction, immune function, and health span (NIH Research Matters)

Dietary Restriction (NIA)

What Do We Know About Healthy Aging? (NIA)

Calorie Restriction and Fasting Diets: What Do We Know? (NIA)

Live Long in Good Health: Could Calorie Restriction Mimetics Hold the Key? (NIA)

Geroscience: The Intersection of Basic Aging Biology, Chronic Disease, and Health (NIA)

Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) (NIA)