In a small study of older adults, researchers at the USC Leonard Davis School of Gerontology have found that people who closely keep to the Mediterranean diet tend to carry higher blood levels of two tiny proteins made inside the cell's mitochondria, the energy-producing structures that have long been with us. Those proteins, humanin and SHMOOSE, have been linked in earlier work to guarding the heart and brain, and the diet itself has been tied for decades to lower risk of heart disease and cognitive decline. The finding offers a possible molecular thread connecting what people eat to how thei
Mediterranean Diet Linked to Higher Mitochondrial Microproteins Tied to Heart and Brain Protection
From observing associations to understanding causality
Mark
So what did they actually find?
Mimi
That older adults who stuck closely to a Mediterranean diet had higher blood levels of humanin and SHMOOSE, and lower oxidative stress markers.
Mark
Why do those two proteins matter?
Mimi
Both have been tied in earlier work to heart and brain protection. Cohen's lab discovered both, humanin in 2003 and SHMOOSE more recently.
Luke
Worth noting that Cohen is a senior author on a study about proteins his own lab found. That's not a flaw, but it's context.
Mark
What about specific foods?
Mimi
Olive oil, fish and legumes lined up with humanin. Olive oil and fewer refined carbohydrates lined up with SHMOOSE.
Luke
Lined up is the key phrase. It's observational and relatively small. The report gives no sample size, so I can't tell you how firm those food links are.
Mark
And the Nox2 finding?
Mimi
Higher humanin went with lower activity of Nox2, an enzyme that makes harmful reactive oxygen species. The authors suggest humanin may reduce oxidative stress.
Luke
Suggest, yes. Nothing here shows the diet raises these proteins, or that raising them prevents disease. That's exactly what the next studies are meant to test.
Le Pouls
- A new blood-based signal suggests the Mediterranean diet may work through mitochondrial microproteins that shield the heart and brain.
- Older adults who followed the diet most closely showed higher humanin and SHMOOSE alongside lower markers of oxidative stress.
- Olive oil, fish and legumes stand out as foods linked to humanin, while olive oil and fewer refined carbohydrates connect to SHMOOSE.
- The study is small and observational, so it cannot yet show the diet raises these proteins or that they prevent disease.
- Researchers are preparing dietary interventions to test whether changing what people eat directly lifts these microproteins and reduces risk.
In a small study of older adults, researchers at the USC Leonard Davis School of Gerontology have found that people who closely keep to the Mediterranean diet tend to carry higher blood levels of two tiny proteins made inside the cell's mitochondria, the energy-producing structures that have long been with us. Those proteins, humanin and SHMOOSE, have been linked in earlier work to guarding the heart and brain, and the diet itself has been tied for decades to lower risk of heart disease and cognitive decline. The finding offers a possible molecular thread connecting what people eat to how their cells age, though it describes an association rather than proof that the diet is the cause.
Researchers at the USC Leonard Davis School of Gerontology have offered a possible explanation for something long observed: why the Mediterranean diet appears to protect the heart and brain. Their study, published in Frontiers in Nutrition, examined blood samples from older adults whose adherence to the diet varied. Those who followed it most closely carried higher levels of two mitochondrial microproteins, humanin and SHMOOSE, and lower markers of oxidative stress, a process widely considered a driver of aging and chronic disease.
The microproteins come from the research of Pinchas Cohen, the school's dean, whose work over more than twenty years helped establish the field of mitochondria-derived peptides. Humanin was first identified in 2003 and has been associated with cardiovascular protection, insulin sensitivity and preserved cognition. SHMOOSE, discovered later, appears to shield neurons from amyloid-related damage. The study also hints that humanin may curb Nox2, an enzyme that produces harmful reactive oxygen species, suggesting a dual route by which the diet might protect the cardiovascular system.
The lead author, Roberto Vicinanza, describes these proteins as possible messengers that translate food into cellular function and aging. Olive oil, fish and legumes were linked to humanin, while olive oil and less refined carbohydrate were linked to SHMOOSE. The authors are careful about the limits: the study is modest in size and observational, showing association rather than cause. The next step is to test whether dietary changes can directly raise these microproteins, and whether doing so reduces disease risk.
Researchers at the USC Leonard Davis School of Gerontology have found a possible molecular clue to why the Mediterranean diet seems to protect the heart and brain. The study, published in Frontiers in Nutrition, found that older adults who closely follow the diet carry higher blood levels of two mitochondrial microproteins, humanin and SHMOOSE. Both have been linked in earlier research to protection against cardiovascular disease and neurodegeneration.
The work was led by Roberto Vicinanza, an instructional associate professor of gerontology at USC Leonard Davis. The senior author was Pinchas Cohen, the school's dean and a USC Distinguished Professor. The team analyzed blood samples from older adults whose adherence to the diet varied. Those with the highest adherence showed significantly elevated humanin and SHMOOSE, along with lower markers of oxidative stress, which is considered a key driver of aging and chronic disease.
Specific foods appeared to matter. Olive oil, fish and legumes were associated with higher humanin. For SHMOOSE, olive oil and a lower intake of refined carbohydrates were the linked factors. The diet itself, built around olive oil, fish, legumes, fruits and vegetables, has long been tied to lower risk of heart disease, diabetes and cognitive decline, though the mechanisms have remained incompletely understood. Cohen said the findings suggest particular components of the diet may directly influence mitochondrial biology, and that humanin and SHMOOSE could serve as biomarkers of adherence with clinical significance.
The microproteins come out of Cohen's own research, which spans more than two decades and helped establish the field of mitochondria-derived peptides. Unlike conventional proteins encoded in nuclear DNA, these are produced from small open reading frames in the separate mitochondrial genome, regions once thought to be nonfunctional. Cohen and colleagues first identified humanin in 2003. It has since been associated with better insulin sensitivity, cardiovascular protection, longevity and preserved cognition. His lab later discovered SHMOOSE, short for Small Human Mitochondrial ORF Over SErine tRNA. A genetic variant of it has been tied to higher Alzheimer's risk, while the normal form appears to shield neurons from amyloid-related damage.
The study also points to a possible interaction between humanin and Nox2, an enzyme that generates harmful reactive oxygen species. Higher humanin levels went along with lower Nox2 activity, suggesting the peptide may help curb oxidative stress and protect the cardiovascular system. The researchers propose a dual mechanism: the diet may lower oxidative stress directly while also raising microproteins that suppress damaging pathways further. Vicinanza called this a possible new cardioprotective mechanism of the diet. He described the microproteins as potential molecular messengers that translate what people eat into how cells function and age.
Vicinanza is also active in public advocacy. He has worked with the Municipality of Pollica in Italy, a UNESCO Mediterranean Diet emblematic community, to help establish an International Day of the Mediterranean Diet at the United Nations. The observance will be held each year on November 16 to raise awareness of the diet's health, cultural and environmental benefits. He argues that eating patterns with little or no ultra-processed food reflect how humans have eaten over long periods, and may create conditions to which mitochondria, ancient cellular organelles, are likely adapted.
The limits are plain. The study was relatively small and observational, so it shows association, not cause. It cannot say that the diet raises these microproteins, or that higher levels reduce disease. The authors see it as a step toward precision nutrition, in which biomarkers like these might help tailor diets for health and longevity.
Next, researchers plan to test whether dietary interventions can directly raise humanin, SHMOOSE and related peptides, and whether such changes lower disease risk. Vicinanza said the goal is to move from observing associations to understanding causality.
Citations marquantes
These microproteins may act as molecular messengers that translate what we eat into how our cells function and age.— Roberto Vicinanza, USC Leonard Davis School
Humanin and SHMOOSE could serve as biomarkers for adherence to the Mediterranean diet and have clinical significance.— Pinchas Cohen, USC Leonard Davis School dean and senior author
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