Does Calorie Restriction Work in Humans to Prolong Life?

What can rodent results tell us about the use of caloric restriction to prolong human lifespan? Well, if a 50 percent lifespan increase could be replicated in people that could increase the current life expectancy up to around 120, but that’s based on experiments that restricted food intakes between 40 and 60 percent starting immediately after weaning. Here’s a chart of expected years of life extension for more modest restrictions, started later in life based on the same body of evidence. So cutting down one’s intake from 2,500 calories a day to 1,750, a 30 percent drop, for a few decades starting in one’s 40’s could potentially add a few years to your life, or even just down to 2,125 calories starting in one’s 30’s. Again, though, this is assuming one can extrapolate from mice and rats, to people. 
 
A study of 41 strains of mice found that caloric restriction shortened the lifespans of twice as many strains than it extended. Cutting food intake 40 percent, one of the most common experimental regimens, extended the lifespans of some strains of male or female mice, but shortened lifespans in twice as many, and had no significant effect on the majority. In one strain, the longevity of female mice was increased while that of male mice was decreased. If we can’t even extrapolate the effects of caloric restriction from one strain of mouse to another strain of mice, how can we extrapolate from mice to men or women? 
 
A meta-analysis of caloric restriction experiments only found about 20 percent of animal species tested experienced life extension, (7 out of 34) but this included all of the mammals: rats, mice, dogs, and monkeys. The effect seemed most pronounced with animals who had been housed in laboratory conditions for generations. For example, food restriction can increase or decrease the lifespans of inbred mice, but appears to have little effect on mice plucked from the wild. Laboratory strains have often been subjected to strong genetic selection for rapid growth, perhaps sensitizing them to the effects of dietary restriction.  
 
Another condition of lab life that limits our ability to extrapolate to people is the fact that rodents are typically raised in pathogen-free conditions. So even if caloric restriction had a strong countervailing impairment of immune function (or wound healing or bone strength), this might not necessarily become apparent under controlled conditions. 
 
Rodents also have starkly different metabolisms than we do. This becomes especially apparent when trying to extrapolate from studies on intermittent fasting. Gram for gram, the metabolic rate of mice is seven times that of humans. So a 24 hour fast in mice equates to closer to a week-long fast in people. Rodents have such high metabolisms that skipping a single day of eating can starve away as much as 15 percent of their lean body mass and fasting for more than forty-eight hours can be deadly. 
 
Psychological states may even influence the effects of caloric restriction. Laboratory animals being food restricted are “convinced” that sustenance is scarce. Their bodies and minds are united in the stress of scarcity. But give fruit flies the impression of abundance by calorie restricting them in the presence of the smell of food, and they lose nearly half the life extension benefits. Even though part of their sensory array was getting clear calorie deficit cues, in the presence of the food aroma their bodies evidently weren’t completely convinced and so never completely committed to the survival reprogramming. What impact might that have on human calorie restriction? Even those stoically able to chronically restrict their diets surrounded by cheap tasty calories, on some level their body would still see abundance everywhere and perhaps may not fully kick into the famine survival mode necessary for full life-extension benefits. 
 
One important critique of the entire field is that even the most successful studies show less the life-extending effects of caloric restriction than the life-shortening effects of obesity. The control group animals in most caloric restriction experiments are allowed to eat ad libitum, meaning eat as much as they want. So maybe any benefits researchers find are less about restricting, and more about just not overeating.  
 
As anyone with pets knows, if you allow then to eat as much as they want, they can get fat. Middle-aged Labrador retrievers given unlimited food access end up with over 20 pounds of body fat and only live about 11 years. If you pair litter puppies and restrict them to eat three quarters of what their ad libitum sibling eats, they put on less than 10 pounds of fat and live an average of 13 years. 37.5 percent the diet restricted dogs survived past the time all their unrestricted siblings had died. Is that evidence that caloric restriction is good or just evidence that obesity is bad? 
 
Ironically, this aspect of the experiments may make them more generalizable to the human populace. Even by five or six years ago, about three-quarters of the US adult population was overweight or obese. So using ad libitum controls may indeed be the appropriate comparator. Those who are very obese throughout their adult lives (BMI over 35) lose about 7 years of life and 19 years of healthy life. Obviously caloric restriction would be good for them, but most of the restriction experiments don’t offer insight into whether someone who is already ideal weight would benefit from restricting further.