Age-related diseases—including cardiovascular disease, cancer and diabetes—are a growing problem worldwide as people live longer lives. Promoting healthy aging is important, but the best intervention for healthy aging identified so far—eating fewer calories (calorie restriction)—is often too difficult for people to follow.

A potential alternative lies in the growing realization that “a calorie is not just a calorie” and that when we eat and what we eat may matter just as much or more than how many calories we consume. I recently explored this concept in the webinar “Quality, Quantity and Timing: Regulating Healthspan and Lifespan with Diet,” where I discussed how our eating patterns regulate metabolism and aging.

Heidi Pak, a student in my lab, is studying how restricting calories promotes healthy aging and long life. Many cultures and popular diet plans incorporate intermittent fasting. Fasting for about half the day has been shown to be beneficial for mice, who, when fed a calorie-restricted diet, eat very rapidly and then fast for most of the rest of the day and night. We found that this prolonged fast was necessary for calorie restriction to improve insulin sensitivity, reduce frailty and extend lifespan. We also found that fasting is enough to provide many of the same metabolic benefits we saw in the mice who followed the calorie-restricted diet.

We also looked at how dietary composition affects health and aging. A typical human diet is made up of fat, protein and carbohydrates. Carbs have gotten a bad reputation, and many people think it’s better to follow a high-protein, low-carb diet.

In work led by former graduate student Nicole Richardson, PhD, we studied dietary levels of three branched-chain amino acids (BCAAs), which are important building blocks of protein. We found that lower levels promote health, fitness and lifespan. Male, but not female, mice who ate less BCAAs had reduced frailty and extended lifespan. Richardson and another former graduate student Deyang Yu, PhD, found that the health benefits from eating fewer BCAAs were primarily the result of reducing levels of one specific BCAA, isoleucine. Higher isoleucine levels are also associated with higher body mass index and higher rates of type 2 diabetes in people.

The bottom line: When thinking about lifespan and healthspan, we may want to rethink what we eat and select lower BCAA foods. We are working to design lower BCAA diets. We may want (with the approval of our health care team) to rethink when we eat too because how long we spend between meals may be very important for health.