Carly Cassella, Science Alert, May 16, 2022
Low-protein diets appear to have incredible benefits for the health and lifespans of rodents, fruit flies, and yeast.
A new study in mice has now identified a single hormone that is essential for these curious anti-aging effects.
The hormone is called fibroblast growth factor 21 (FGF21), and it is secreted by the liver.
In recent years, studies have shown that FGF21 responds to protein restriction in male mice, improving energy expenditure and glucose tolerance while reducing body weight.
Now, the same team of researchers has found FGF21 is required for the anti-aging effects, too.
"Indeed, mice that are FGF21 deficient are not only resistant to the health [benefits] of [protein restriction], but they also exhibit early-onset weight loss, increased frailty, and reduced lifespan when fed a low-protein diet," the authors write.
The new findings suggest that the pro-longevity effects of protein restriction are dependent on a single hormone - one that is also present in humans.
Whether FGF21's role in our own species is the same as in mice is currently unclear, but studies on humans show that diets low in protein and high in carbohydrates could have similar benefits for metabolic health. These macronutrients also impact circulating FGF21.
Studies among mice are helping scientists better understand the role this hormone plays in the body.
When male mice had their FGF21 gene knocked out and then were fed a low-protein diet, their natural lifespan was reduced compared to normal mice fed the same diet.
The mice without the FGF21 gene generally grew up to be larger and less lean. Researchers say they had "completely lost" their tolerance for glucose. As these mice began to naturally age, they also started losing weight much earlier, becoming frailer faster than those with their FGF21 genes intact.
Even to the naked eye, researchers say the adult mice producing FGF21 looked healthier and more physically robust on a long-term low-protein diet. Their coats were not nearly as shabby or patchy as the mice without the FGF21 gene.
In short, the findings suggest that protein restriction reduces frailty in normal mice as they age, and that this process is controlled via the FGF21 signaling pathway.
FGF21 has a lot of roles, but is known to regulate sugar intake, and the way this hormone responds to certain macronutrients has an impact on the brain.
Previous research by the same authors has shown that long-term low-protein diets increase FGF21 activation in the mouse brain, leading individuals to choose foods lower in fat and carbohydrates and higher in protein when given multiple options.
"Our data suggest that FGF21 talks to the brain, and that without this signal the mouse doesn't 'know' that it is eating a low-protein diet. As a result, the mouse fails to adaptively change its metabolism or feeding behavior," explains neuroscientist Christopher Morrison from Louisiana State University.
The findings offer a possible explanation for why restricted protein intake can improve the lifespans of mice. But it's important to note that this study was only focused on male animals. Female mice may not have as strong a response to similar diets.
Still, the study is the first to identify a single hormone that controls for the beneficial effects of a low-protein diet.
The study was published in Nature Communications.
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