A new study from researchers at the USC Leonard Davis School of Gerontology suggests that some of the well-known health benefits of the Mediterranean diet may be explained by tiny proteins found inside our cells’ mitochondria. These small proteins, called mitochondrial microproteins, appear to play an important role in how diet influences ageing and the risk of disease. The findings offer a fresh perspective on how what we eat can affect the body at a very fundamental, cellular level.
The research, led by Roberto Vicinanza, found that people who closely follow a Mediterranean-style diet tend to have higher levels of two specific microproteins, humanin and SHMOOSE. Both have been linked to protection against heart disease and conditions affecting the brain. According to the researchers, these microproteins may act as messengers, helping to translate dietary habits into changes in how cells function and age. This could help explain why the Mediterranean diet has such a strong reputation for supporting long-term health.
The Mediterranean diet, which emphasises foods such as olive oil, fish, legumes, fruits, and vegetables, has long been associated with lower risks of cardiovascular disease, diabetes, and cognitive decline. However, the biological mechanisms behind these benefits have not been fully understood. In this study, researchers analysed blood samples from older adults with different levels of adherence to the diet. Those who followed the diet most closely had higher levels of humanin and SHMOOSE, along with lower levels of oxidative stress, which is a key contributor to ageing and chronic illness.
The study also found that specific foods within the diet may have distinct effects. For example, olive oil, fish, and legumes were linked to higher levels of humanin. In comparison, olive oil combined with a lower intake of refined carbohydrates was associated with higher levels of SHMOOSE. These findings suggest that not just the overall dietary pattern, but also particular food choices, may directly influence mitochondrial function and overall health.
Mitochondrial microproteins are a relatively new area of scientific interest. Unlike most proteins, which are produced from DNA in the cell nucleus, these are encoded within the mitochondria themselves. Some regions of mitochondrial DNA were once thought to have no real function, but scientists now know they can produce important molecules like humanin. This microprotein has already been linked to improved insulin sensitivity, cardiovascular protection, and better cognitive function. SHMOOSE, discovered more recently, has been connected to brain health, with certain genetic variations linked to a higher risk of Alzheimer’s disease.
Another important finding from the study is that higher levels of humanin were associated with lower activity of an enzyme called Nox2, which produces harmful molecules that contribute to oxidative stress. This suggests that the Mediterranean diet may protect the heart through multiple pathways, both by reducing harmful processes and by boosting protective ones. Although the study was relatively small and observational, it points towards the possibility of using these microproteins as biomarkers to guide personalised nutrition strategies. Future research will explore whether changing diet can directly increase these protective proteins and whether that leads to measurable improvements in health and longevity.
More information: Roberto Vicinanza et al, Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin–Nox2 interaction in cardioprotection, Frontiers in Nutrition. DOI: 10.3389/fnut.2025.1727012
Journal information: Frontiers in Nutrition Provided by University of Southern California
