Researchers at the USC Leonard Davis School of Gerontology have found that following the Mediterranean diet is associated with higher levels of mitochondrial microproteins, which contribute to cardiovascular and neuronal health. The study, published in Frontiers in Nutrition, shows that individuals who adhere more closely to this diet have increased levels of humanin and SHMOOSE, proteins known for their role in protecting against cardiovascular disease and neurodegeneration, along with lower biomarkers of oxidative stress.

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Roberto Vicinanza, MD, PhD, the first author and an associate professor at USC, stated that these microproteins may serve as molecular messengers, translating dietary intake into cellular function and aging. This research builds on extensive work related to mitochondria led by Pinchas Cohen, MD, the dean of the school.

Humanin and SHMOOSE, which are encoded in mitochondrial DNA, have been studied for their roles in insulin sensitivity, vascular protection, cognitive preservation, and modulation of Alzheimer’s disease risk. The study analyzed blood samples from 49 older adults, linking adherence to the Mediterranean diet with higher circulating levels of these microproteins, suggesting they may mediate the diet's health benefits. The researchers noted a potential connection between Humanin signaling and Nox2 activity, a finding that hints at a new cardioprotective mechanism associated with the diet.

The Mediterranean diet emphasizes whole grains, fruits, vegetables, legumes, olive oil, and fish, while reducing red meat and refined carbohydrates. These foods provide various bioactive compounds that influence inflammation and mitochondrial function. The study identified that olive oil intake positively correlated with both microproteins, while fish and legumes were specifically linked to humanin levels. A lower intake of refined carbohydrates correlated with higher levels of SHMOOSE.

The researchers suggest that the levels of these microproteins may reflect the body’s bioenergetic responses to specific dietary patterns of the Mediterranean diet. They connected these effects to biochemical pathways influencing aging and health, including SIRT1 activation and AMPK signaling enhanced by omega-3 fatty acids.

Humanin has been noted for its ability to reduce oxidative stress and improve endothelial function, crucial for vascular health. The study identified an inverse relationship between humanin levels and markers indicative of oxidative stress, suggesting its role in reducing inflammation.

In neurological health, both microproteins have shown protective effects against amyloid-related toxicity. Previous findings from Cohen’s lab have demonstrated that these proteins can mitigate neurotoxicity induced by amyloid-β, complementing research that associates the Mediterranean diet with improved cognitive outcomes.

While the benefits of the Mediterranean diet on oxidative stress and cardiovascular health have been documented, this study highlights the under-researched role of mitochondrial microproteins in these processes. It opens the door for future investigations into the significance of humanin and SHMOOSE in dietary adherence and biological response, as well as potential personalized dietary interventions aimed at aging and disease prevention.