Large mouse study reveals new details about how eating less can extend lifespan

For nearly a century, laboratory studies have shown consistent results: eat less food, or eat less often, and an animal will live longer. But scientists have struggled to understand why these types of restrictive diets help extend lifespan and how best to implement them in humans.

Now, in a highly anticipated study appearing in the October 9 issue of NatureScientists from the Jackson Laboratory (JAX) and their collaborators tracked the health of nearly 1,000 mice on various diets to make new advances in these questions.

The study was designed to ensure that each mouse was genetically distinct, allowing the team to better represent the genetic diversity of the human population. In doing so, the results become more clinically relevant, elevating the study to one of the most important investigations of aging and lifespan to date.

The study concluded that eating fewer calories had a greater impact on lifespan than periodic fasting, revealing that very low-calorie diets generally extended the lifespan of mice, regardless of their body fat levels. or glucose, both generally considered markers of metabolic health and aging.

Surprisingly, the mice that lived the longest on restrictive diets lost the least weight despite consuming less. The animals that lost the most weight on these diets tended to have low energy, compromised immune and reproductive systems, and shorter lives.

“Our study really highlights the importance of resilience,” said Gary Churchill, the Karl Gunnar Johansson Chair and professor at JAX who led the study.

“The most robust animals maintain their weight even in the face of stress and calorie restriction, and they live the longest. This also suggests that a more moderate level of calorie restriction may be the way to balance health long term. and lifespan.

Churchill and his colleagues assigned female mice to one of five different diets: one in which the animals could freely eat any amount of food at any time, two in which the animals received only 60% or 80%. of their baseline calories each day, and two in which the animals received no food for one or two consecutive days each week but could eat as much as they wanted on other days.

Then the mice were studied for the rest of their lives with periodic blood tests and a thorough assessment of their overall health.

Overall, mice on an unrestricted diet lived an average of 25 months, those on an intermittent fasting diet lived an average of 28 months, those eating 80% of their basal diet lived an average of 30 months and those who consumed 60% of their basic diet lived. for 34 months.

But within each group, the range of lifespans was wide; Mice eating the fewest calories, for example, had lifespans ranging from a few months to four and a half years.

When the researchers analyzed the rest of their data to try to explain this wide range, they found that genetic factors had a much greater impact on lifespan than diet, highlighting how underlying genetic traits , yet to be identified, play a major role in how these genetic factors. diets would affect an individual’s health trajectory.

Additionally, they identified genetically encoded resilience as a critical factor in lifespan; Mice that naturally maintained their body weight, body fat percentage, and immune cell health during periods of stress or low food intake, as well as those that did not lose body fat late in life, survived the longest.

“If you want to live a long life, there are things you can control over the course of your life, like diet, but what you really want is a very old grandmother,” Churchill said.

The study also casts doubt on traditional ideas that certain diets can prolong life. For example, factors such as weight, body fat percentages, blood sugar, and body temperature do not explain the link between calorie reduction and longer life. Instead, the study found that immune system health and red blood cell-related traits were more clearly linked to lifespan.

Importantly, these findings mean that human studies of longevity, which often use metabolic measures as markers of aging or youth, might overlook more important aspects of healthy aging.

“Although calorie restriction is generally good for lifespan, our data shows that losing weight through calorie restriction is actually bad for lifespan,” Churchill explained.

“So when we look at human trials of longevity drugs and see that people are losing weight and having better metabolic profiles, it turns out that may not be a good marker of how long they last at all. of future life.”