Researchers in Japan have discovered that boosting a protein called COX7RP in mice improves mitochondrial function, leading to longer lives and better health. The engineered mice lived 6.6% longer on average, with enhanced metabolism and reduced signs of aging. This finding points to potential ways to promote healthier aging in humans.
A team of scientists has uncovered a promising approach to slowing cellular aging by optimizing the efficiency of mitochondria, the cell's energy producers. Led by Satoshi Inoue of the Tokyo Metropolitan Institute of Geriatrics and Gerontology, and co-authored by Kazuhiro Ikeda of Saitama Medical University, the study focused on the protein COX7RP, which aids in forming mitochondrial respiratory supercomplexes. These structures enhance energy production while curbing harmful reactive oxygen species that contribute to oxidative stress.
The researchers developed transgenic mice (COX7RP-Tg) that overproduced COX7RP throughout their lives. Compared to normal mice, these animals not only extended their lifespan by 6.6% but also displayed markers of improved healthspan. They exhibited better glucose regulation through increased insulin sensitivity, lower levels of blood triglycerides and total cholesterol, enhanced muscle endurance, and reduced fat accumulation in the liver.
At the cellular level, tissues from the COX7RP-Tg mice showed greater assembly of supercomplexes and higher ATP output. In white adipose tissue, the mice had elevated coenzyme NAD+ levels, decreased reactive oxygen species, and lower β-galactosidase, a hallmark of cellular senescence. Single-nucleus RNA sequencing revealed suppressed activity in genes linked to age-related inflammation, including those involved in the senescence-associated secretory phenotype (SASP).
"We previously identified COX7RP... as a key factor that promotes the formation of mitochondrial respiratory supercomplexes, thereby enhancing energy production and reducing reactive oxygen species," Inoue explained. The study, published in Aging Cell, suggests that targeting these mechanisms could yield new therapies for age-related conditions like diabetes, dyslipidemia, and obesity. "Our study elucidated novel mitochondrial mechanisms underlying anti-aging and longevity," Inoue added, hinting at future applications through supplements or drugs that bolster supercomplex function.
This research builds on growing interest in mitochondria as a target for extending not just lifespan, but the quality of life in later years. While promising in mice, human applications will require further validation.
