Protein Restriction Linked to FGF21 Hormone and Longevity in Mammals

Recent scientific research has examined how reducing dietary protein affects metabolism and longevity in mammals, focusing on the hormone FGF21. Studies have explored these effects in both animal models and human participants.

Multiple peer-reviewed studies report that limiting protein in the diet increases the amount of FGF21 circulating in the blood of mice, rats, and humans. FGF21 is recognized as a hormone that coordinates the body's response to protein restriction by triggering adaptive metabolic and behavioral changes.

In research involving male mice, scientists found that a protein-restricted diet led to longer lifespans, reduced frailty, lower body weight, and improved glucose tolerance. These benefits only occurred when FGF21 was present, indicating the hormone's essential role in mediating the positive effects of protein restriction.

Further investigation using mice that lack FGF21 showed that protein restriction did not produce the same metabolic improvements. Instead, these mice experienced early weight loss, increased frailty, and shorter lifespans, highlighting the necessity of FGF21 for beneficial outcomes from protein restriction.

What the numbers show

• In human studies, a five-week protein-restricted diet increased fasting plasma FGF21
• Male mice with FGF21 showed lifespan extension on protein restriction
• Mice without FGF21 did not gain metabolic benefits from protein restriction

In human clinical studies, lean and healthy men who followed a protein-restricted diet for five weeks experienced higher fasting plasma FGF21 levels. These participants also needed to consume more calories to maintain their body weight during the period of protein restriction.

Reviews of dietary restriction mechanisms have found that protein restriction not only stimulates FGF21 secretion but also suppresses nutrient-sensing pathways such as mTORC1. Additionally, this dietary approach lowers levels of IGF-1, another hormone involved in growth and metabolism.

Researchers have noted that protein restriction can reproduce many of the effects seen with calorie restriction, such as improved metabolic health and longevity. However, these effects occur through distinct biological pathways that specifically involve FGF21, rather than simply reducing overall energy intake.

FGF21 has been identified as a central factor in the body's adaptation to low-protein diets, acting as an endocrine signal to coordinate the necessary metabolic and behavioral responses. This role has been observed across different mammalian species, including humans, mice, and rats.

* This article is based on publicly available information at the time of writing.