The lifespan extension caused by a low-protein diet appears to be coordinated by a single hormone.
Recent research from the Pennington Biomedical Research Center discovered that reducing protein in the diet resulted in a variety of positive health outcomes, including an increase in lifespan, and that these effects are dependent on Fibroblast Growth Factor 21 (FGF21), a liver-derived metabolic hormone.
The study was published in the journal Nature Communications.
It is indeed long known that eating less improves health and extends life, and there has been growing interest in the possibility that eating less protein or amino acids contributes to this positive effect. Numerous recent studies have suggested that low-protein diets, but not to the point of malnutrition, can improve health. Overconsumption of high-protein diets, on the other hand, has been linked to an increase in mortality in certain age groups.
The metabolic hormone FGF21 was discovered to be a major signal connecting the body to the brain during protein restriction a few years ago by Pennington Biomedical’s Neurosignaling Laboratory. When young mice were fed a low-protein diet without this signal, they did not change their feeding behavior or metabolism.
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.”
Christopher Morrison PhD, Professor and Director, Neurosignaling Lab, Pennington Biomedical Research Center
The team’s most recent study, headed by postdoctoral researcher Cristal M. Hill, PhD, shows that low-protein diets improve metabolic health, reduce frailty, and extend lifespan in aged mice.
These positive effects were also seen when middle-aged mice’s protein intake was reduced, even protecting them from the negative effects of obesity. These positive effects were lost in mice lacking FGF21, implying that FGF21’s action in the brain is essential for increased health and longevity.
We previously showed that FGF21 acts in the brain to improve metabolic health in young mice fed a low-protein diet. These new data extend this work by demonstrating that FGF21 also improves metabolic health and extends lifespan. Collectively, these data provide clear evidence that FGF21 is the first known hormone that coordinates feeding behavior and metabolic health to improve lifespan during protein restriction.”
Cristal M. Hill, Pennington Biomedical Research Center
However, several questions remain, according to Dr Hill. It is indeed unclear how these findings will apply to aging people, but the hope is that this research will uncover new molecular and neural pathways that can be used to improve people’s health.
This groundbreaking research has important implications for extending the health and lifespan of people. If scientists can better understand how diets and nutritional hormones like FGF21 act to extend lifespan, these discoveries could offset many of the health issues that occur in middle age and later.”
John Kirwan PhD, Executive Director, Pennington Biomedical Research Center
Hill, C. M., et al. (2022) FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice. Nature Communications. doi.org/10.1038/s41467-022-29499-8.