Mitochondrial Respiratory Supercomplex Assembly Factor COX7RP Contributes to Lifespan Extension in Mice

Area of Science:

• Mitochondrial biology
• Aging research
• Metabolic homeostasis

Background:

• COX7RP is crucial for mitochondrial respiratory chain supercomplex assembly, impacting energy production efficiency.
• Its role in metabolic homeostasis and lifespan extension is not well understood.

Purpose of the Study:

• To investigate the function of COX7RP in metabolic homeostasis and its effect on lifespan.
• To explore the molecular mechanisms underlying COX7RP's influence on aging and longevity.

Main Methods:

• Utilized COX7RP-transgenic (COX7RP-Tg) mice for phenotypic analysis.
• Performed glucose tolerance tests (GTT) and measured serum lipid profiles (triglyceride and total cholesterol).
• Assessed cellular energy markers (ATP, NAD+), oxidative stress (ROS), and senescence markers (β-galactosidase).
• Conducted single-nucleus RNA-sequencing (snRNA-seq) on white adipose tissue (WAT).

Main Results:

• COX7RP-Tg mice demonstrated significantly extended lifespan.
• Metabolic improvements included lower post-GTT blood glucose and reduced serum triglyceride and total cholesterol.
• Elevated ATP and NAD+ levels, decreased ROS production, and reduced senescence markers were observed.
• snRNA-seq revealed downregulation of senescence-associated secretory phenotype genes in WAT of old COX7RP-Tg mice.

Conclusions:

• COX7RP is a key factor in extending lifespan and promoting metabolic health.
• COX7RP influences aging resistance by modulating senescence pathways in adipose tissue.
• This study highlights COX7RP's potential as a therapeutic target for aging and longevity.