Recent research published in journals Frontiers of nutrition Our findings suggest that the health benefits of the Mediterranean diet may come from small proteins produced within the energy-producing structures of cells. Researchers found that older adults who adhered to such a diet had higher levels of two microscopic proteins that protect against heart disease and cognitive decline. These results provide a new biological explanation for how a diet rich in olive oil, fish, and legumes promotes healthy aging at the cellular level.
To understand the mechanisms behind these physiological benefits, it helps to look inside human cells. Most people are familiar with mitochondria, which act as microscopic power plants that produce the energy needed for cell survival. Mitochondria contain their own set of genetic instructions, completely separate from the main DNA housed in the cell nucleus.
For many years, geneticists believed that this particular small piece of mitochondrial DNA had no practical purpose. During the Human Genome Project, researchers largely missed these small genetic sequences. It seemed too short to encode a functional molecule. Scientists eventually realized that these genetic codes actually produce active molecules called mitochondrial microproteins.
Although these microproteins are much smaller than standard cellular proteins, they play important roles in regulating cell health and responding to stress. Two specific microproteins known as Humanin and SHMOOSE have attracted attention for their powerful protective properties. Previous studies have linked humulin to improved insulin sensitivity, cell survival, and protection against cardiovascular disease.
Similarly, SHMOOSE appears to help protect brain cells from the type of structural damage commonly seen in Alzheimer’s disease. Because mitochondria are deeply involved in how the body processes nutrients, the researchers wondered if daily eating habits might influence the production of these protective microproteins. Roberto Bicinanza, an associate professor of education in gerontology at the University of Southern California, led a team investigating this possibility.
Pinchas Cohen, dean of the Leonard Davis School of Gerontology at the University of Southern California, served as lead author on the project. Vicinanza and his colleagues wanted to find out whether distinct levels of humanin and schmoose are present in the blood of people who follow a traditional Mediterranean diet. The Mediterranean diet emphasizes whole grains, fruits, vegetables, legumes, and olive oil, and limits red meat and highly processed carbohydrates.
Medical experts widely recommend this dietary pattern to prevent metabolic disorders and maintain overall cardiovascular function. The researchers also aimed to measure markers of oxidative stress, a biological process that damages cells and accelerates aging. When mitochondria produce energy, they naturally produce reactive oxygen molecules as a byproduct, just as a car engine produces exhaust gas.
When the body produces too many of these reactive molecules, it causes oxidative stress, often driven by an enzyme known as Nox2. Researchers hypothesized that a healthy diet may increase levels of small proteins, which in turn help suppress this harmful oxidative activity.
To test these ideas, researchers recruited 49 older adults from a cardiovascular clinic in Rome, Italy. The participants, whose average age was about 78 years old, were originally part of a large-scale observational program focused on heart rhythm disorders. Medical staff asked patients to complete a standardized dietary questionnaire detailing their typical eating habits at home.
The survey awarded participants points based on how often they consumed staple foods such as olive oil, fish, fruits, and vegetables. Based on the final score, the researchers divided the patients into two different groups. One group had high adherence to the Mediterranean diet, while the other group had low to moderate adherence.
The clinical team then took fasting blood samples from all participants and measured circulating levels of humanin and SHMOOSE. They also analyzed the blood for two specific chemical markers that indicate the presence of oxidative stress in cells. The laboratory staff evaluating the samples did not know which dietary group each patient belonged to, which helped prevent observational bias during the testing phase.
When researchers compared blood test results and dietary scores, they noticed a clear physiological pattern. Patients who strictly followed a Mediterranean diet had elevated concentrations of both humus and schmoose in their bloodstream. Conversely, the low dietary adherence group had relatively low levels of these microscopic proteins.
When basic lipid profiles such as total cholesterol and triglycerides were compared between the two groups, the results were not statistically significant. However, differences in microprotein concentrations were clearly striking across patient cohorts.
The researchers then analyzed individual food components to see which items had the strongest physiological effects. They found that patients who consumed at least one tablespoon of olive oil daily and ate minimal amounts of refined white bread had the highest levels of schmoozing. On the other hand, increased humanin levels were found in patients who regularly consumed olive oil, fish, and several servings of legumes each week.
“These microproteins may act as molecular messengers that translate what we eat into how our cells function and age,” Bicinanza said. He noted that this newly observed biological pathway helps explain why this particular dietary pattern is so effective in maintaining physical health over the long term.
In addition to the increase in microproteins, the researchers observed an inverse relationship between humanin and Nox2, an enzyme responsible for cell damage. Patients with higher levels of circulating humanin had lower levels of Nox2 activity and fewer markers of overall oxidative stress. This inverse correlation suggests that Humin may actively prevent enzymes from producing harmful oxygen molecules in the bloodstream.
Cohen noted that these small proteins are emerging as important regulators of aging biology. “Research may link mitochondrial function to diseases such as Alzheimer’s disease and heart disease, and potentially to nutrition,” Cohen said. Researchers believe this diet may have the dual benefit of providing natural plant-based antioxidants while fortifying protective microproteins.
Although this data provides new perspectives on nutrition and cellular health, the authors acknowledge that their study has some limitations. The project is based on an observational design and cannot definitively prove that diet directly caused changes in microprotein levels. The relatively small number of participants and their specific age range also means that the results may not automatically apply to younger people or the wider population.
Furthermore, the dietary questionnaire provided an abbreviated snapshot of dietary habits rather than a comprehensive record of daily dietary intake. The researchers did not track other lifestyle factors, such as daily physical activity, which may also affect mitochondrial function and overall metabolic health. The participants also had moderate underlying health conditions, which may have affected how their bodies naturally produce these proteins.
Future studies will require controlled dietary interventions to confirm these initial observations. In these upcoming projects, scientists will actively change participants’ diets over a period of time and measure the resulting changes in microprotein levels. If the current findings are replicated in clinical trials, medical professionals could eventually use Humanin and SHMOOSE as simple blood markers to track how well patients adhere to nutritional advice.
The researchers ultimately hope to translate these biochemical findings into personalized nutritional plans that slow the aging process. By understanding exactly how certain foods interact with cells’ mitochondria, doctors may one day be able to prescribe highly tailored diets that maximize cellular protection. Until then, the study reveals another biological reason to prioritize whole grains, olive oil, and legumes at your dinner table.
The study, “Adherence to the Mediterranean diet is associated with the mitochondrial microproteins humin and SHMOOSE; the potential role of humin and Nox2 interaction in cardioprotection,” was authored by Roberto Vicinanza, Vittoria Cammisotto, Junxiang Wan, Kelvinyen, Francesco Violi, Pasquale Pignatelli, and Pinchas Cohen.
