New Study: Olive Leaf Extract Could Counter Muscle Aging by Boosting Mitochondria

Highlights: 

• Muscle samples from older donors show calcium-related mitochondrial defects that correlate with low muscle mass and strength. 
• Dietary olive leaf extract improves mitochondrial function, running time, and muscle weight in aged mice.

Our mitochondria produce the energy needed to sustain life. This is why mitochondrial dysfunction is a hallmark of aging, contributing to chronic diseases like sarcopenia — age-related muscle decline. While some anti-aging molecules like NAD+ precursors can help prevent chronic diseases indirectly by maintaining mitochondria, a new study shows that mitochondria can be targeted directly with molecules from olive leaves. 

In a preprint from BioR_Xiv, Gherardi and colleagues from University of Padova in Italy and the Nestlé Institute of Health Sciences report that mitochondrial calcium uptake declines during aging. Additionally, a reduction in a key gene for calcium uptake is correlated with reduced muscle mass and strength in sarcopenia patients. Finally, olive leaf extract is shown to increase calcium uptake and improve the physical performance of aged mice. 

Olive Leaf Extract Improves Calcium-Related Mitochondrial Dysfunction

With every voluntarily movement, our muscles (skeletal muscles) contract. During contraction, calcium ions (Ca²⁺) are driven into our mitochondria, leading to increased energy production. Increased energy production is important because low energy contributes to reduced muscle mass and strength, clinical features of sarcopenia that impact physical autonomy and quality of life. 

To determine if reduced mitochondrial Ca²⁺ intake could contribute to sarcopenia, Gherardi and colleagues examined muscle cells from young and aged donors. To simulate muscle contraction, the researcher exposed the cells to caffeine, which induces Ca²⁺ release. They then measured mitochondrial Ca²⁺ uptake with a light-sensitive dye. The results showed that mitochondrial Ca²⁺ uptake was reduced by 45% in aged individuals. 

A lack of mitochondrial Ca²⁺ uptake in muscle during contraction would suggests lower energy production. This blunted energy production could help explain the low muscle mass and strength that characterize sarcopenia. To support this idea, Gherardi and colleagues analyzed genes from sarcopenia patient muscle samples. They found that a gene for regulating mitochondrial Ca²⁺ transport called MCUR1 was reduced. 

For Ca²⁺ to get into mitochondria, it must flow through a transporter called the mitochondrial calcium uniporter (MCU), which is regulated by MCU regulator 1 (MCUR1).  Thus, a reduction in MCUR1 could explain why mitochondria are unable to uptake as much Ca²⁺ in muscle from older individuals. Furthermore, the researchers showed that low MCUR1 mRNA is associated with low muscle mass and low grip strength in sarcopenic patients, suggesting that impaired mitochondrial Ca²⁺ uptake contributes to sarcopenia. 

To identify possible therapies for targeting reduced mitochondrial Ca²⁺ uptake, Gherardi and colleagues screened for natural molecules that increase mitochondrial Ca²⁺ uptake. Based on its bioavailability and safety profile, a molecule called oleuropein, found in olive plants, was chosen. Oleuropein was found to increase mitochondrial Ca²⁺ uptake in muscle cells from aged donors. 

To test the effect of oleuropein supplementation, Gherardi and colleagues fed aged (24 month) mice 50 mg/kg/day of olive leaf extract (OLE) with high levels of oleuropein. OLE restored mitochondrial activity, suggesting increased energy production, and improved the running time and muscle weight of the aged mice. These findings suggests that OLE could counter aspects of muscle aging (sarcopenia), such as reduced endurance and muscle size by increasing mitochondrial Ca²⁺ uptake.

Olives and Aging   

Gherardi and colleagues are the first to show that mitochondrial Ca²⁺ uptake is reduced in aged muscle. This means more studies will be needed to confirm the therapeutic value of oleuropein for sarcopenia. The authors say: 

“Given the history of safe human use of oleuropein and polyphenol/olive-rich diets, our discovery opens exciting translation to clinical trials and applications for prevention and medical management of sarcopenia and other age-related diseases.”

It should be pointed out that Nestlé sells olive oil extract through two of their daughter companies, Persona and Solgar. However, olive leaf extract is widely available in supplement form from other companies. Oleuropein is in olive fruits themselves, meaning it can be found in olive oil. Along with oliv