16 April 2022, Saxony-Anhalt, Kathendorf: The full moon rises behind a forest in the early evening. ...

Of Mice and Men

For mice, fasting at the right time extended lifespans — but can it work for humans?

Studies on animals, usually lab mice, have limited applications to humans.

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Restricting calories and eating only when their bodies were most primed to metabolize the food seemed to impart on lab mice unique life-extending benefits, at a molecular and genetic level — benefits that caloric restriction alone did not, according to a new study published Thursday in Science.

What’s New — Mice whose calories were cut by 30 percent of what they would usually eat lived 10.5 percent longer than a control group of mice with no caloric restrictions. Another grouping, that had the same calorie restrictions but was fed during daylight hours, lived 20 percent longer than the control group.

The mice that lived the longest in the study were put under the same caloric restriction and were only fed at night, the active time in the nocturnal animals’ internal circadian clocks. They lived 34 percent longer than the control group. This feeding regiment also seemed to activate genes that were not activated in any of the other groups.

The life-extending effects of caloric restriction and fasting on mice have been well documented but not completely understood. Carol Yepes/Moment/Getty Images

The control group, which was allowed an all-you-can-eat buffet of pellets whenever they wanted via automated feeders, were subjected to neither caloric restriction nor fasting, both of which have repeatedly been shown to extend lifespans in lab mice. Expectedly, that group died soonest (at a median of 792 days or roughly 2 years).

The next shortest-lived group of mice (at a median of 875 days) got the benefit of caloric restriction. Then the second longest-lived group (which lived about 950 days) got the benefits of both caloric restriction and fasting. The most long-lived group (at about 1,050 days) received the benefits of caloric restriction, fasting, and fasting at an optimal time for their metabolism. With each tweak, the lifespan lasted longer.

All mouse groups that endured caloric restriction developed the usual diseases of old age significantly later in life than their control group counterparts. They also had less body fat and fewer signs of inflammation, but something at a molecular level seemed to be happening only to the mice forced to fast until night. They experienced fewer changes in gene expression with age and there were 68 genes that were specifically protected within that group.

“Our entire metabolism in our bodies has been programmed to deal with this nutrition when we’re active”

Although further study is needed, the benefits of a combination of caloric restriction and limiting eating to prime metabolic hours could extend the lifespans of several species, including humans, Joseph Takahashi, one of the authors, tells Inverse.

“Our entire metabolism in our bodies has been programmed to deal with this nutrition when we’re active,” says Takahashi, a neurobiologist at the University of Texas Southwestern Medical Center. “If you look at the liver, at all of our metabolic tissues, they have these incredible daily patterns of metabolism.”

There could be a right and a wrong time of day to eat, and using the short lifespans of lab mice, some researchers say they can see the accrued lifetime benefit of eating at the right time.

How They Did It — The researchers only used male mice of the same genetic makeup to ensure the homogeny of the mice.

They actually tried six feeding patterns. The mice fed only during the day and those fed only during the night were subdivided into groups whose feed times were limited to two hours and to 12 hours, but those fasting durations didn’t make much of a difference in outcome.

The researchers also kept track of the mice’s exercise, in case any feeding pattern led mice to have more time and energy for running on wheels, which could color the results by improving the mice’s health, but all mice groups exercised about equally.

Why It Matters — From the paper:

Because of these direct links among the pathways involved in aging and longevity, metabolism and the circadian clock, our results demonstrate the importance of timing and [caloric restriction] and indicate that optimizing the phase of circadian gene expression may be a powerful intervention for extending lifespan.

Does that include the lifespan of humans? That’s still unclear.

Time-restricted eating has been studied in both lab animals and people. The trade-off between the two is this: Studies on animals, usually lab mice, have limited applications to humans, which is generally the species that interests health researchers as an end game.

But studies on humans can’t measure the effect this eating pattern would have on longevity. Clinical trials of intermittent fasting on humans tend to look at weight loss or athletic performance and they have had some middling outcomes. But if limiting the metabolic reaction to eating to a certain window of time each day has the benefits at the cellular level and in circadian rhythms that some researchers think it does, those benefits would play out at a molecular level over a lifetime.

Intermittent fasting has been popular in recent years, but studies on the effects on humans have been middling.Shutterstock

There is no practical way to run that kind of decades-long experiment on humans. As such, the matter remains unresolved and people continue to hype up its benefits, even when the science is far from clear.

“Obviously, mice and in humans are different,” says Takahashi. “But there are also many commonalities. This increase in inflammation that occurs with age, it also happens in people... Mice and humans are pretty similar at the level of the genes, but obviously, our physiology is different. We live way longer than a mouse. So there are additional factors that are going on with human aging.”

Overall, he says, “It's a little premature to say that there's no value in what we find in the mouse to human health there.”

What’s Next — Of course, Takahashi and his team plan to examine the specific genes that seem to be upregulated by the caloric restriction/fasting/eating-only-at-night combo more closely and see if they offer insight into the mice’s extended lifespans.

Also, this paper only reported results from examinations of the liver. He also wants to study how these differences in feeding approaches would impact muscle, fat, and brain tissue.

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