Some Evidence-Based Answers to Your Frequently-Asked Questions: A 3-Part Series

Part 2: Fasting, caloric restriction, and aging

By Eric Verdin, President and CEO of the Buck Institute

This is Part 2 of our series, “Some Evidence-Based Answers to Your Frequently-Asked Questions,” where I answer the most common questions we get about steps you can take to help you live better longer, using up-to-date data and scientific research. In Part 1, we explored the health benefits of exercise on aging. Today, I will discuss a topic which has received a lot of attention over the years: caloric restriction and intermittent fasting.

What are caloric restriction and intermittent fasting, and should I being doing that?

Caloric restriction is one of the first and best-known interventions to slow aging.  Caloric restriction is defined as the reduction of caloric intake without malnutrition; calories are typically reduced by about 20-40%. It has been found to extend the lifespan and slow the development of age-related health decline in a variety of laboratory model animals including fruit flies, worms, mice, rats, and rhesus monkeys, though the effect is not universal. The health and longevity benefits of caloric restriction in humans, however, are still unclear. Lower caloric intake has been observed to correlate with improved lifespan and healthspan in certain human populations such as the Okinawa “blue zone” (regions of the world where people live longer than average). However, it is unknown whether these increases in longevity are due purely due to caloric intake or to other factors including environment, activity levels, and genetics.

Caloric restriction seems to act on a variety of cellular pathways.  Unsurprisingly, many of these pathways are linked to the biological aging process. Model animals on caloric restriction have down-regulated TOR (the cell’s master energy sensor), improved insulin sensitivity, resistance to oxidative stress and inflammation, and enhanced cellular repair. It is hypothesized that reduced caloric intake triggers cellular pathways that promote survival during times of low nutrient availability in the wild, leading to enhanced cellular maintenance and repair.

While research on the effects of caloric restriction in humans is ongoing, one of the first studies to directly tackle this question (published in April 2018) showed some promising results. It demonstrated that reducing calories by 15% for two years in healthy, non-obese adults decreased the resting metabolic rate and reduced cellular stress and damage, both of which are linked to age-related neurological conditions such as Alzheimer's and Parkinson's diseases, as well as to cancer and diabetes. This study suggests that some of the health benefits of caloric restriction observed in model organisms may be conserved in humans, but longer-term studies are needed to determine whether these changes affect disease risk and longevity as well.

There is also some evidence that it is not only how much you eat, but when you eat that may affect health and aging. Intermittent fasting, which can include time-restricted feedings such as limiting food intake to an 8- to 12-hour period each day or alternate day caloric restriction, has been shown to have several health benefits in laboratory animals similar to what is seen in caloric restriction, including reduced cellular stress and damage and decreased aging-related health decline. A few studies in humans have suggested that intermittent fasting may lead to enhanced weight loss. Maintaining a healthy weight is certainly a key to healthy aging, but there is currently no scientific consensus on the health and longevity effects of intermittent fasting in humans. Short-term periods of no/low calories can also trigger the same cellular pathways found in caloric restriction.

Caloric restriction and intermittent fasting sometimes prove challenging for people to maintain due to the physical discomfort of hunger, social timing of meals, and other factors. New studies are looking at ways to target the downstream pathways associated with these dietary restrictions to potentially gain these long-term health benefits in a more sustainable, effective way.

In summary, there is a solid body of evidence that caloric restriction and intermittent fasting can increase healthy longevity in a variety of model animals. These dietary interventions seem to work by activating cellular maintenance and repair pathways to help cells maintain a healthier state. There is very limited evidence in humans, but it suggests that these benefits likely extend to people, too. Research into these interventions continues in both humans and model animals, with one of the goals being the development of therapeutics that can target those same pathways without adopting a low-calorie lifestyle. If you are interested in pursuing either caloric restriction or intermittent fasting, talk to your doctor about how it might work within your own personal health context.

Stay tuned for next month, the third and final installment in our Evidence-Based Answers to Your Frequently-Asked Questions.