A new study led by researchers at the University of Southern California’s Leonard Davis School of Gerontology suggests that some of the benefits of the Mediterranean diet may come from tiny proteins hidden within mitochondria, opening new doors to how diet shapes aging and disease risk.
The study, led by Roberto Vicinanza, the Leonard Davis Supervising Associate Professor of Gerontology at the University of Southern California, found that people who adhered to a Mediterranean-style diet had higher levels of two mitochondrial microproteins, humulin and SHMOOSE, both of which are associated with protection against cardiovascular disease and neurodegeneration.
These microproteins may act as molecular messengers that translate what we eat into how our cells function and age. This is a new biological pathway that helps explain why the Mediterranean diet is so powerful. ”
Roberto Vicinanza, Associate Professor of Gerontology Education, Leonard Davis School of Gerontology, University of Southern California
diet, mitochondria, aging
A Mediterranean diet rich in olive oil, fish, legumes, fruits, and vegetables has long been associated with a lower risk of heart disease, diabetes, and cognitive decline. However, the mechanisms behind these benefits remain to be elucidated.
In the new study, researchers analyzed blood samples from older adults with varying levels of dietary adherence. Those with the highest adherence showed significantly elevated levels of humanin and SHMOOSE, along with lower markers of oxidative stress, a key factor in aging and chronic disease.
The research team also found that certain foods appeared to be important. Olive oil, fish, and legumes were associated with increased humanin levels, and decreased intake of olive oil and refined carbohydrates was associated with increased SHMOOSE.
“These findings suggest that certain components of the Mediterranean diet can directly influence mitochondrial biology,” said Pinchas Cohen, USC Leonard Davis Dean and lead author of the study. “Humanin and SHMOOSE may serve as biomarkers of adherence to the Mediterranean diet and are clinically important.”
New roles for mitochondrial microproteins
The study builds on more than 20 years of research led by Cohen, a pioneer in the discovery of mitochondrial-derived peptides.
Unlike traditional proteins encoded by nuclear DNA, these microproteins are produced from small open reading frames in separate mitochondrial genomes that were once thought to be non-functional.
Among the most well-studied substances is humanin, first identified in 2003 by Cohen et al. It has since been associated with improved insulin sensitivity, cardiovascular protection, longevity, and preserved cognitive function.
More recently, Cohen’s lab discovered SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), a microprotein associated with brain health. Genetic variants of SHMOOSE are associated with increased risk of Alzheimer’s disease, while the normal form is thought to protect neurons from amyloid-related damage.
“These peptides are emerging as key regulators of aging biology,” Cohen said. “They could link mitochondrial function to diseases such as Alzheimer’s and heart disease, and potentially even nutrition.”
Linking diet and heart protection
Another notable finding from this study is the potential interaction between humanin and Nox2, an enzyme that produces harmful reactive oxygen species.
Increased humanin levels were associated with decreased Nox2 activity, suggesting that this peptide may help reduce oxidative stress and protect the cardiovascular system.
The researchers propose that the Mediterranean diet may work through a dual mechanism: directly lowering oxidative stress while increasing mitochondrial microproteins that further suppress damaging pathways.
“This may indicate a new cardioprotective mechanism of the Mediterranean diet,” Bicinanza said.
From the lab to global advocacy
Outside the lab, Mr. Vicinanza is also active in promoting the Mediterranean diet on the global stage, linking his scientific research to broader international efforts to promote the Mediterranean diet as a model for health, culture and sustainability. He worked with Italy’s Municipality of Polica, the UNESCO Mediterranean Diet Symbol Community, and helped establish the International Day of the Mediterranean Diet at the United Nations. The event is held on November 16th every year and aims to raise awareness of the health, cultural and environmental benefits of food around the world. Its broad mission is consistent with research findings, he said.
“We are combining centuries-old food traditions with cutting-edge molecular biology,” Bicinanza said. “This study supports the idea that healthy dietary patterns with little or no ultra-processed foods reflect how humans have been eating over time and may create conditions for mitochondria (ancient cell organelles) to adapt.”
Aiming for precise nutrition and healthy aging
Although the study was relatively small and observational, the findings represent a new frontier in “precision nutrition,” in which biomarkers such as mitochondrial microproteins can help tailor diet to optimize health and longevity.
Future studies will investigate whether dietary interventions can directly increase levels of humanin, SHMOOSE, and related peptides, and whether these changes lead to reduced disease risk.
“Our goal is to move from observing associations to understanding causation,” Bicinanza said. “If we can harness these pathways, we may be able to design nutritional strategies that promote healthy aging at the molecular level.”
sauce:
University of Southern California
Reference magazines:
Bicinanza, R. Others. (2026). Adherence to the Mediterranean diet is associated with the mitochondrial microproteins humulin and schmoose. Potential role of Humanin-Nox2 interaction in cardioprotection. Frontiers of nutrition. DOI: 10.3389/fnut.2025.1727012. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1727012/full
