Researchers monitored the health of almost a thousand mice following various diets to determine whether these diets could help extend their lifespans. The study ensured that all mice were genetically different to better reflect the human population’s genetic variety. This approach enhances the clinical relevance of the findings, making this investigation one of the most important studies on aging and lifespan conducted so far.
For nearly a hundred years, laboratory experiments have consistently indicated that consuming less food or eating less frequently can lead to a longer life for animals. Yet, scientists have faced challenges in understanding why these restrictive diets promote longevity, and how they can be effectively applied to humans. Now, a long-anticipated study published in the Oct. 9 issue of Nature by scientists at The Jackson Laboratory (JAX) and their collaborators seeks to provide new insights into these questions.
The research was carefully structured to include genetically diverse mice, allowing better representation of human genetics. This approach enhances the clinical relevance of the study, establishing it as one of the most valuable investigations into aging and lifespan so far.
The findings revealed that consuming fewer calories significantly influenced longevity more than intermittent fasting. Very-low-calorie diets generally increased the mice’s lifespans, regardless of their body fat or glucose levels—both of which are usually considered indicators of metabolic health and aging. Surprisingly, the mice that survived the longest on restrictive diets tended to lose the least weight despite their reduced food intake. Conversely, those who shed the most pounds on these diets displayed lower energy levels and weakened immune and reproductive systems, resulting in shorter lifespans.
“Our study highlights the significance of resilience,” stated Gary Churchill, the lead researcher and a professor at JAX. “The hardiest mice maintained their weight even when facing stress and caloric limitations, making them the longest-lived. This suggests that a moderate level of calorie restriction could be the balance between maintaining long-term health and lifespan.”
Churchill and his team assigned female mice to five different dietary groups: one allowing unlimited food access, two with daily intakes of 60% or 80% of their usual calories, and two with fasting for either one or two days each week while eating freely on other days. The mice were then observed throughout their lives, receiving regular blood tests and comprehensive health evaluations.
Mice on unrestricted diets had an average lifespan of 25 months, those on intermittent fasting lived for about 28 months, while those consuming 80% of their baseline calories averaged 30 months, and those on 60% of their baseline lived for 34 months. However, there was a considerable lifespan variability within each group; some mice on the lowest calorie intake lived anywhere from just a few months up to four and a half years.
Upon analyzing the data for potential explanations for this variability, researchers found that genetic factors significantly influenced lifespan more than diet, underlining the role of yet-to-be-identified genetic features in how diets affect individual health trajectories. They identified genetically based resilience as crucial for longevity; mice that consistently maintained their body weight, fat levels, and immune cell health during periods of low food availability, or those that did not lose fat as they aged, lived the longest.
“If you want to have a long life, there are controllable factors like diet, but honestly, what you really want is to have a very old grandmother,” Churchill commented.
The study challenged conventional beliefs about why specific diets promote longevity. For instance, traditional markers like weight, body fat percentages, blood glucose levels, and body temperature didn’t clarify the relationship between calorie reduction and lifespan extension. Instead, the research established a clearer link between immune system health and certain characteristics of red blood cells with longevity. This indicates that human studies on longevity, often relying on metabolic indicators as signs of youthfulness or aging, may be overlooking more crucial aspects of healthy aging.
“While caloric restriction generally supports increased lifespan, our data suggest that weight loss as a result of caloric restriction can actually be detrimental to lifespan,” Churchill explained. “Thus, when examining human trials of longevity medications that show weight loss and improved metabolic profiles, it’s possible those factors are not good indicators of future lifespan.”
