- A study in mice suggests that the timing of meals is important to maximize the anti-aging effects of calorie restriction.
- On a calorie-restricted diet, mice that only ate during the active phase of their circadian cycle lived nearly 35% longer than control mice that ate whenever they wanted.
- Mice on a calorie-restricted diet that ate only during their inactive phase lived only 10% longer than the control mice.
- If the findings hold true for humans, they suggest that to maximize lifespan people should reduce their calorie intake and avoid eating late at night.
Studies in worms, flies, rodents, and monkeys have demonstrated that diets that severely restrict total calorie intake, while providing all the essential nutrients, extend average lifespan.
The research shows that in all these organisms, food shortages trigger physiological changes that promote longevity and delay the onset of age-related disease.
Animal studies have revealed that timing of calorie restriction can have an effect due to the circadian system, which controls daily cycles of physiology, metabolism, and behaviors such as eating. This has also been linked to aging.
This led researchers at the University of Texas (UT) Southwestern Medical Center in Dallas, TX, to investigate whether the timing of meals contributes to the life-extending effects of calorie restriction.
Numerous studies have shown that calorie restriction increases the average lifespan of mice. But most of this research has involved scientists feeding calorie-restricted diets to laboratory mice during the day.
Unlike humans, mice are nocturnal, which means they have evolved to feed at night.
So for their study, the scientists used automatic feeders to ensure that some of the mice ate only during the night.
To determine whether the timing of meals had an effect on lifespan — independently of calorie restriction and fasting — they split the animals into 6 groups.
In one group, which served as a control, the animals could eat ad libitum (as much as they wanted, whenever they wanted).
The remaining 5 groups ate calorie-restricted diets (30–40% fewer calories) with the same total calorie intake but different feeding schedules.
Control mice that ate ad libitum had a median lifespan of 800 days, whereas mice on a calorie-restricted diet with food available around the clock lived 875 days, or 10% longer.
Mice on the calorie-restricted diet that ate only during the day (the inactive phase of their circadian cycle) and fasted for 12 hours overnight lived 959 days. In other words, they lived almost 20% longer than the controls.
But calorie-restricted mice that only ate during their active phase, then fasted for the remaining 12 hours, lived the longest. These animals clocked up an average 1,068 days of lifespan, which was nearly 35% longer than the control animals.
The scientists have reported their findings in Science.
“We have discovered a new facet to caloric restriction that dramatically extends lifespan in our lab animals,” says senior author Dr. Joseph Takahashi, Howard Hughes Medical Institute Investigator and chair of neuroscience at UT Southwestern Medical Center.
“If these findings hold true in people, we might want to rethink whether we really want that midnight snack,” he adds.
They also found that calorie-restricted diets improved the animals’ regulation of glucose levels and insulin sensitivity, but the improvements were greatest for mice that ate only at night (their active phase).
This suggests that the mice were healthier and aged more slowly, Dr. Takahashi told Medical News Today.
The researchers found that, in all the mice, aging increased the activity of genes involved in inflammation and decreased the activity of genes involved in metabolism and circadian rhythms.
Calorie restriction slowed down these age-related changes, but mice that only ate a night reaped the greatest benefits.
“Since aging can be considered a progressive ramping up of inflammation, [calorie restriction] is also delaying this age-related increase in inflammation, which is also consistent with delaying the aging process,” said Dr. Takahashi.
The authors note some limitations of their study.
In particular, they write that sleep disruption in the mice that ate during the day (during their inactive phase) may have contributed to their shorter lifespan.
In addition, all the mice in the study were male. The authors write that in females, ovarian hormones may provide some protection against disruptions in circadian rhythms.
As with all research that involves animal models, the study may not translate well to humans.
If the findings do apply to humans, which have the opposite active phase to mice, the scientists suggest that eating early in the evening is best for healthy aging.
One day it may even be possible to develop drugs that target circadian genes or the proteins that they make, in order to mimic the anti-aging benefits of eating only during the active phase.
“[W]e are working on this idea and searching for drugs that can enhance circadian alignment,” said Dr. Takahashi. “Fingers crossed!”
Eating late at night interferes with the body’s ability to keep blood sugar levels within a healthy range.
A recent study found this was particularly true for people with a particular variation of the gene for the melatonin receptor.
Melatonin is a hormone that helps to govern the sleep-wake cycle. As its levels increase in the evening, this not only triggers sleepiness but also impairs insulin secretion.
As a result, the body has more difficulty controlling blood sugar levels after meals close to bedtime.
“Since many people opt for carbohydrate-rich snacks in late evenings, such as chips, cookies, candy, or popcorn, these snacks are more likely to impair blood sugar control and increase one’s risk for prediabetes and diabetes,” said Mariam Eid, R.D., L.D., a dietitian and founder of A Happy AOneC, which advises teens and young adults recently diagnosed with prediabetes.
“Therefore, consuming carbohydrate-rich meals and snacks earlier in the day promotes better blood sugar balance and supports the prevention of prediabetes and diabetes,” she told MNT.