A modified diet that takes cues from the Mediterranean model has the potential to promote healthier aging, with scientists combining a large dataset from human research with the results of an animal study to understand the mechanisms at play.
Led by Valter Longo from the University of Southern California's (USC) Davis School of Gerontology, in collaboration with the University of Toronto and Harvard University, the researchers looked at existing data on 200,000 people to determine whether their health status could be tied to their diet.
They found that a low-protein, amino acid-supplemented eating plan – one that's largely plant-based, with the addition of fish and a small amount of eggs and dairy – was associated with a longer lifespan, as well as lower fat mass and reduced frailty risk.
The team applied their observational findings to a mouse model to see whether the diet directly affected the rodents' lifespan independent of other factors.
“We expected different diets to produce different outcomes, but what really impressed us was how modulating just a single amino acid, methionine, in the longevity diet could produce such dramatic metabolic changes,” said first author Maura Fanti, a USC Leonard Davis research associate. “It points to the idea that amino acid composition, not just overall protein quantity, may be the target of strategic metabolic interventions.”
Longo noticed that southern Europe’s long-lived populations, who appeared to age more healthily, largely ate a plant-heavy Mediterranean diet. The diet provided a small amount of methionine and other essential amino acids, but perhaps not enough, because the population also has a high rate of frailty.
So despite having some of the highest life expectancies across the globe, these older adults were not immune to age-related health issues.
Longo then developed a longevity diet, with added methionine, to see if it could have a measurable impact on frailty.
Using an animal model, researchers assigned 20-month-old mice one of four assigned meal plans: a standard diet, a Western diet high in fats and sugars, a low-carbohydrate ketogenic diet, and a low-protein, methionine-supplemented "longevity" diet.
Ultimately, mice on the longevity diet had meaningfully better health markers, including reduced fat mass, lower frailty, and an overall healthier lifespan.
While the mouse model is a clear limitation, the researchers want to adapt it for a human trial to test their findings.
“There are, of course, differences in how these pathways are regulated between mice and humans, but seeing such coordinated changes across multiple metabolic hormones is genuinely encouraging, and we're very curious to know whether effects of similar magnitude would be seen in human studies,” Fanti says.
Interestingly, the mice on this longevity meal plan were able to eat more calories yet still lost fat while maintaining lean body mass, but only when methionine levels were low but sufficient.
Tests on the mice also revealed biomarkers of better cardiometabolic health in this cohort, including greater activity of signaling molecules that affect metabolism, such as GLP-1.
“This challenges the dogma that calorie reduction is necessary to lose weight, but it also tells us that we need to have a clear understanding of the mechanisms,” Longo adds. “Too little methionine caused frailty, but too much methionine abolished the benefits of this diet, which was otherwise based on the diet of long-lived populations like the traditional Italian and Okinawa diets.
"These results indicate that overall protein intake may be less important than specific amino acid intake," the scientist adds.
The researchers' theory about there being a kind of "Goldilocks Zone" when it came to methionine was supported by additional human data. Earlier studies found that limiting methionine intake in mice – so the animals got enough, but not as much as they would with a high-protein diet – promoted fat loss and reduced the risk of type 2 diabetes.
In the data gathered by the USC researchers, they found that people who ate high amounts of animal protein – and, as a result, also consumed a high amount of methionine and other essential amino acids – were more likely to be obese and had double the risk of type 2 diabetes than individuals who ate little to no animal protein. This was a constant, even when diets were calorie-restricted and otherwise healthy and balanced.
While a robust human trial is needed to test preliminary findings, this study paves the way for further investigation into whether there's an essential amino acid "sweet spot" that could impact healthy aging.
The study was published in the journal Cell Metabolism.
Source: University of Southern California via EurekAlert!
Fact-checked by Mike McRae
