People around the world are living longer than ever before, and this change is altering many people’s expectations of ageing. The goal is no longer just to live longer, but to live more good years. As a result, the focus is shifting to the “health span”, the period of life when someone is energetic, independent and generally free from serious age-related problems.
An important focus of these efforts are the mitochondria, which are often referred to as the power plants of the cells. These structures generate the energy that keeps cells running by producing adenosine triphosphate (ATP). Since aging and many age-related diseases are closely linked to declining mitochondrial function, scientists see mitochondria as an important target for research aimed at healthier longevity.
Mitochondrial Supercomplexes and the Energy Pipeline
Within the mitochondria, energy production depends on the respiratory chain complexes. These molecules move protons and electrons in a way that ultimately enables cells to produce ATP. Researchers have known for years that these complexes can assemble into larger, flexible groupings called supercomplexes. It is assumed that these supercomplexes improve the efficiency of mitochondrial respiration.
However, there is little clear evidence directly linking supercomplexes to clear health benefits, particularly from animal studies. This gap has left an important question unanswered: Do these structures actually have a measurable impact on aging and overall health?
The COX7RP Protein Under the Microscope
To investigate this, a team led by Satoshi Inoue from the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan looked at COX7RP, a mitochondrial protein that supports the formation of supercomplexes. Their new study, co-authored by Dr. Kazuhiro Ikeda from Saitama Medical University in Japan, was published 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 increasing energy production and reducing reactive oxygen species (ROS) that cause oxidative stress in cells,” explains Dr. Inoue. “On this basis, we have investigated the role of COX7RP and mitochondrial respiratory supercomplexes in the regulation of ageing and anti-ageing processes.”
Genetically Modified Mice Lived Longer and Stayed Healthier
The researchers developed COX7RP transgenic (COX7RP-Tg) mice to produce higher levels of COX7RP throughout their lives. Using this model, the team was able to track exactly how the protein affected lifespan, age-related changes and metabolism.
The results were impressive. On average, the COX7RP-Tg mice lived 6.6% longer than wild-type mice. The benefits were not limited to lifespan, as the genetically modified mice also showed signs of better healthspan. They had improved glucose homeostasis due to higher insulin sensitivity and improved lipid levels with lower triglycerides and total cholesterol in the blood. The team also noted better muscle endurance and less fat accumulation in the liver.
Stronger Mitochondria and Fewer Ageing Signals
At the cellular level, the data indicated a significant improvement in mitochondrial performance. In tissues from COX7RP-Tg mice, the formation of mitochondrial respiratory supercomplexes increased and ATP production also increased.
A closer examination of white adipose tissue revealed changes in several age-related biomarkers. The mice had higher levels of the coenzyme NAD+, lower levels of ROS and reduced levels of the cellular aging marker β-galactosidase. Using single-core RNA sequencing of the white adipose tissue of older mice, the researchers also found reduced activity of genes associated with age-related inflammation. These included genes associated with the senescence-associated secretory phenotype (SASP), a prototypical feature of senescent cells.
Why this Could be Important for Healthy Ageing
Overall, the findings suggest that increasing the energy efficiency of mitochondria could help delay or reduce common age-related problems. “Our study has elucidated new mitochondrial mechanisms underlying anti-aging and longevity and provided new insights into strategies to promote healthspan and extend lifespan,” Dr. Inoue emphasizes. “For example, dietary supplements and drugs that improve the structure and function of mitochondrial respiratory supercomplexes could contribute to lifespan extension.”
The researchers say that further work could underpin the importance of mitochondrial supercomplexes as treatment targets. If confirmed, this line of research could support new approaches to maintaining vitality and treating age-related metabolic disorders such as diabetes, dyslipidemia and obesity.