Image by pics five/Shutterstock

CtBP2 is a sensor molecule that responds to metabolism. It is known to be associated with obesity. Researchers at University of Tsukuba have discovered that CtBP2 is secreted extracellularly and its activation improves systemic metabolism (promoting health and exerting anti-aging effects). Furthermore, they have demonstrated that blood concentrations of CtBP2 can serve as an indicator with which to estimate general health and the degree of aging.

Tsukuba, Japan—Aging is a systemic process that affects the entire body. Visible external signs of aging usually correspond to evidence of equivalent aging in the functioning of their internal organs. This indicates that skin cells age in tandem with other cells throughout the body, suggesting a mechanism whereby aging in one part of the body spreads systemically.

The Tsukuba research group began focusing on CtBP2 while working to elucidate the mechanisms responsible for obesity. This sensor molecule is known to respond to metabolism, and its activity has previously been reported to decrease in individuals with obesity, leading to metabolic syndrome. Furthermore, the activation of CtBP2 has demonstrated therapeutic effects. The Tsukuba researchers conducted a detailed study of the molecular mechanisms of CtBP2. They found that this molecule, which was previously thought to work inside the cell, is secreted extracellularly when activated. They found that activation improves systemic metabolism and that disruption of this process leads to aging and an increase in health problems. This is in concordance with the simultaneous nature of the aging process throughout the whole body.

Upon establishing a method to measure CtBP2 levels in blood, the researchers found that these levels decrease with age and that individuals from long-lived families have higher blood concentrations of CtBP2. Furthermore, diabetic patients with advanced complications were found to exhibit lower blood CtBP2 levels. This suggests that blood concentrations of CtBP2 could serve as an indicator with which to estimate the degree of aging and overall health status.

These findings are expected to lead to the development of new indicators for general use that will aid in the maintenance of healthy lifestyles. They may also contribute to new anti-aging and health promotion strategies that increase the secretion of CtBP2 into the blood.

###
This work was supported by the Japan Promotion of Science (Grant Numbers 20K08855 and 23K18270 to M.S.), the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP18gm5910007, JP25gm6710004 and JP22ek0210175, Takeda Science Foundation, Ono Medical Research Foundation, Manpei Suzuki Diabetes Foundation and Japan Diabetes Foundation (to M.S.).

Original Paper

Title of original paper:

The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan

Journal:

Nature Aging

DOI:

10.1038/s43587-025-00973-4

Correspondence

Associate Professor SEKIYA Motohiro
Institute of Medicine, University of Tsukuba

Related Link

Institute of Medicine