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People around the world are living longer than ever, and that shift is changing what many want from aging. The goal is no longer just more years, but more good years. That has put new attention on “healthspan,” the stretch of life when someone remains energetic, independent, and generally free of serious age-related problems.
A major focus of this effort is the mitochondria, often called the powerhouse of the cell. These structures generate the energy that keeps cells running by producing adenosine triphosphate (ATP). Because aging and many age-related diseases are closely tied to declining mitochondrial function, scientists see mitochondria as an important target for research aimed at healthier longevity.
Mitochondrial supercomplexes and the energy pipeline
Inside mitochondria, energy production depends on respiratory chain complexes. These molecules move protons and electrons in ways that ultimately allow cells to make ATP. Researchers have known for years that these complexes can assemble into larger, flexible groupings called supercomplexes. These supercomplexes are thought to improve the efficiency of mitochondrial respiration.
Even so, solid evidence that directly connects supercomplexes to clear health benefits has been limited, especially from studies in animals. That gap has left an important question unresolved: do these structures actually make a measurable difference for aging and overall health?
The COX7RP protein under the microscope
To explore this, a team led by Team Leader Satoshi Inouefrom the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan examined COX7RP, a mitochondrial protein that helps supercomplexes form. Their new study, co-authored by Dr. Kazuhiro Ikeda from Saitama Medical University in Japan, appeared in the journal Aging Cell.
“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,” explains Dr. Inoue. “Based on this, we investigated the role of COX7RP and mitochondrial respiratory supercomplexes in regulating aging and anti-aging processes.”
Engineered mice lived longer and stayed healthier
The researchers created COX7RP-transgenic (COX7RP-Tg) mice that were designed to produce higher levels of COX7RP throughout their lives. With this model, the team could closely track how the protein affected lifespan, aging-related changes, and metabolism.
The results were striking. On average, the COX7RP-Tg mice lived 6.6% longer than wild-type mice. The benefits were not limited to lifespan alone, since the engineered mice also showed signs of better healthspan. They had improved glucose homeostasis due to greater insulin sensitivity, as well as improved lipid measures with lower blood triglycerides and total cholesterol. The team also found better muscle endurance and less fat buildup in the liver.
Stronger mitochondria and fewer aging signals
At the cellular level, the data pointed to a clear improvement in mitochondrial performance. In tissues from COX7RP-Tg mice, the formation of mitochondrial respiratory supercomplexes increased, and ATP production rose as well.
A closer look at white adipose tissue revealed shifts in multiple aging-related biomarkers. The mice showed higher levels of coenzyme NAD+, lower levels of ROS, and reduced levels of the cellular aging marker β-galactosidase. Using single-nucleus RNA sequencing on white adipose tissue from older mice, the researchers also found reduced activity in genes associated with age-related inflammation. This included genes tied to the senescence-associated secretory phenotype (SASP), a prototypic characteristic of senescent cells.
Why this could matter for healthy aging
Taken together, the findings suggest that making mitochondria more energy efficient may help delay or reduce common problems linked to aging. “Our study elucidated novel mitochondrial mechanisms underlying anti-aging and longevity, and provided new insights into strategies for promoting healthspan and extending lifespan,” highlights Dr. Inoue. “For instance, supplements and medications that enhance the assembly and function of mitochondrial respiratory supercomplexes may contribute to longevity expansion.”
The researchers say additional work could strengthen the case for mitochondrial supercomplexes as treatment targets. If confirmed, this line of research could support new approaches to preserving vitality and addressing age-related metabolic disorders including diabetes, dyslipidemia, and obesity.
This work was supported by grants of the Japan Society for the Promotion of Science (23K07996, 24K02505, 22K06929, 23H02962, 24K21297); the Integrated Research Initiative for Living Well with Dementia at the Tokyo Metropolitan Institute for Geriatrics and Gerontology; the Takeda Science Foundation; and the Vehicle Racing Commemorative Foundation. This research was also supported by AMED under Grant Number JP25gm2110001.
