A new study led by researchers from the Tokyo Metropolitan Institute for Geriatrics and Gerontology has identified mitochondrial mechanisms that may play a key role in anti-aging and longevity. The research, published in the journal Aging Cell on November 18, 2025, focused on the mitochondrial protein COX7RP and its effect on healthspan and lifespan.
Mitochondria are responsible for producing energy in cells, and their decline is linked to aging and many age-related diseases. Mitochondrial respiratory chain complexes can form supercomplexes, which are thought to improve energy production efficiency. However, there has been limited evidence directly connecting these supercomplexes with health benefits in animal models.
To investigate this further, the team led by Satoshi Inoue examined mice genetically modified to express higher levels of COX7RP throughout their lives. According to Dr. Inoue, "We previously identified COX7RP, a mitochondrial protein, as a key factor that promotes the formation of mitochondrial respiratory supercomplexes, thereby enhancing energy production and reducing reactive oxygen species (ROS) that cause oxidative stress in cells. Based on this, we investigated the role of COX7RP and mitochondrial respiratory supercomplexes in regulating aging and anti-aging processes."
The study found that these transgenic mice had an average lifespan 6.6% longer than wild-type mice. They also showed improved glucose regulation due to better insulin sensitivity, healthier lipid profiles with lower blood triglycerides and cholesterol levels, greater muscle endurance, and less fat accumulation in the liver.
On a cellular level, tissues from these mice demonstrated increased formation of mitochondrial supercomplexes leading to higher ATP production. White adipose tissue analyses indicated improvements in biomarkers associated with aging—such as higher NAD+ levels and reduced ROS—as well as lower expression of genes related to inflammation typically seen in aged cells.
Dr. Inoue emphasized the significance of these findings: "Our study elucidated novel mitochondrial mechanisms underlying anti-aging and longevity, and provided new insights into strategies for promoting healthspan and extending lifespan. For instance, supplements and medications that enhance the assembly and function of mitochondrial respiratory supercomplexes may contribute to longevity expansion."
The authors suggest that future research could help establish mitochondrial supercomplexes as targets for therapies aimed at maintaining vitality or treating age-related metabolic diseases like diabetes or obesity.
