Mice That Eat Less Live Longer – And We May Finally Know Why: ScienceAlert

We’ve known for more than a century that mice and rats live longer when they eat less, but a new study reveals that the secret may be an imbalance between energy consumed and burned, rather than a lack of energy or protein.

American and British researchers studied groups of mice fed identical diets and found that those living in cooler environments lived longer and healthier lives. The major difference was that they had to expend more energy to stay warm.

These findings suggest that limiting research to energy intake per se will not be enough to understand how diet affects health and aging, says the team led by nutritional scientist Daniel Smith of the University of Alabama at Birmingham and biological scientist Sharon Mitchell of the University of Aberdeen in Scotland.

It’s a discovery that could one day allow people to enjoy the same longevity benefits without strict dieting.

“It’s not just caloric intake, macronutrient intake or protein intake or any one component,” Smith told Carolyn Beans for a PNAS Journal Club news article on research.

“It’s the interaction of these in relation to the overall energy balance.”

There is no consensus on the exact mechanism by which calorie reduction is good for rodent health and longevity.

One theory is that the benefits simply come from eating less food or reducing a particular macronutrient. Some research suggests that reducing the intake of certain proteins may be a factor. It’s also possible that a short-term energy imbalance during calorie restriction could lead to long-term health gains.

If the benefits come only from reduced caloric and protein intake, health measures should not vary between different groups of mice if their food intake is the same, the researchers suggested. But if the benefits come from reduced energy availability due to a need to stay warm, then lifespan and health should improve in the “cooler” mice if their food intake matches that of the “warmer” group.

The study allowed groups of mice living in warmer environments to eat food ad libitum for 12 hours a day. Mice living in colder environments were “pair-fed” to match the diets of their warmer counterparts, ensuring the groups received the same calories, protein and other nutrients.

A short-term experiment was conducted on mice kept at 10°C, 21°C, or 30°C for 11 weeks. Biomarker tests showed that mice living in cooler environments experienced hormonal, metabolic, and physiological benefits. They also lost weight relatively quickly and maintained that weight loss.

A longer experiment was conducted on mice from 12 weeks old to the end of their lives. Those kept at 22°C lived about 20% longer than those fed the same diet but kept at 27°C. Mice that lived in cooler cages were also healthier as they aged compared to warmer mice, whose balance, coordination and neurological functions declined more rapidly.

“Thus, energy balance (energy intake minus energy expenditure) was the main contributor to the observed benefits,” the team writes.

The cooler temperatures created an energy imbalance for this study without the effects being influenced by medication or exercise, but the cold itself may have its own influence. Of course, most humans won’t find it practical to brave the cold to cause an energy imbalance, and we don’t know if it’s good for us.

Researchers wonder whether other factors, such as certain medications, might also improve health by unbalancing the body’s energy. It remains to be seen whether GLP-1 analog drugs, such as Ozempic, can lead to similar long-term improvements.

“These results provide strong evidence that dietary energy intake alone is not necessary to predict health benefits and longevity of sustained dietary interventions,” the authors conclude.

The research was published in the journal GeroScience.