A "longevity diet" centered on plant-based foods with supplemental fish, characterized by low protein and carefully balanced levels of the amino acid methionine, improved healthspan and reduced frailty in mice, according to a study published in Cell Metabolism. Researchers from the University of Southern California (USC), supported by human data from over 200,000 people, suggest that specific amino acid composition—rather than total protein quantity—may be a primary driver of metabolic health and longevity.
Impact of Methionine on Aging and Frailty
Researchers at the USC Leonard Davis School of Gerontology, led by senior author Valter Longo, investigated how modifying dietary amino acid intake influences aging. While traditional plant-based diets in regions like southern Europe are associated with long life expectancies, they are also linked to higher rates of frailty in old age. Because plant proteins naturally contain lower levels of essential amino acids compared to animal products, the team tested a modified "longevity diet" (LDMM) that included a controlled amount of methionine.
In the study, 20-month-old mice fed the LDMM—a low-protein, methionine-supplemented diet—outperformed those on standard, Western, or ketogenic diets. According to first author Maura Fanti, these mice experienced longer healthspans, reduced body fat, and lower levels of frailty. The researchers observed that modulating a single amino acid produced significant metabolic changes, suggesting that the precise composition of amino acids is a vital target for metabolic intervention.
Metabolic Markers and Hormone Regulation
The study found that the LDMM improved cardiometabolic health markers in mice, including increased levels of GLP-1, a hormone involved in metabolic regulation. Notably, this improvement occurred even though the LDMM group consumed more food and equal total calories compared to other groups.
"Seeing such coordinated changes across multiple metabolic hormones is genuinely encouraging," Fanti said. The researchers highlighted that these benefits appeared only when methionine levels were kept low but sufficient, suggesting a narrow therapeutic window for the amino acid.
Human Data and Dietary Patterns
To validate these findings, the research team analyzed dietary and health data from more than 200,000 individuals. The findings indicated that participants with the highest intake of animal protein—and consequently higher levels of methionine—were twice as likely to have Type 2 diabetes and exhibited higher rates of obesity compared to those consuming little or no animal protein.
Longo noted that these health discrepancies persisted even when individuals with high animal protein intake consumed fewer total calories. This finding challenges the conventional emphasis on simple calorie restriction, pointing instead toward the importance of specific nutrient profiles. The team plans to move forward with controlled clinical trials in humans to determine if the benefits observed in the LDMM model translate to human populations.
Research Team and Disclosures
The study was a collaborative effort involving the USC Leonard Davis School of Gerontology, the University of Toronto, Harvard University, the University of Campinas, the Keck School of Medicine of USC, and Children’s Hospital Los Angeles. Funding was provided by the National Institute on Aging (grant AG084485), the National Institute of Health (grant GR1045540), and the USC Edna Jones Chair Fund.
Regarding potential conflicts of interest, Valter Longo holds an equity interest in L-Nutra, a company developing medical foods. Longo, Todd Morgan, and Sebastian Brandhorst have filed patents related to the Fasting-Mimicking Diet through USC, which has licensed intellectual property to L-Nutra. Additionally, Longo and Fanti are inventors on a U.S. provisional patent application related to the methods and findings described in the study.