A hidden blood molecule may hold the secret to healthy aging and long life

Aging affects every part of the body, inside and out. The wrinkles and gray hair that appear on the surface often mirror similar changes happening deep within our organs. This connection suggests that aging does not occur in isolation but instead spreads throughout the body in a coordinated way. In other words, when one system begins to age, others may follow.

A research team at the University of Tsukuba turned its attention to a molecule called CtBP2 while studying the biological links between obesity and metabolism. CtBP2 acts as a sensor that responds to metabolic changes, and earlier research had shown that its activity declines in people with obesity, which can contribute to metabolic syndrome. Interestingly, stimulating or activating CtBP2 has been shown to produce therapeutic effects that improve metabolism.

The Tsukuba scientists explored CtBP2 in greater depth to understand its molecular behavior. They discovered that this molecule, once believed to function only inside cells, is actually released outside the cell when activated. When CtBP2 is active and present in the bloodstream, it helps maintain healthy metabolism across the body. However, when its activity is disrupted, it can trigger systemic aging and an increase in health-related issues. This finding supports the idea that aging occurs as an interconnected, body-wide process rather than a series of isolated events.

After developing a method to measure CtBP2 levels in blood samples, the researchers observed that these levels tend to decline with age. People from long-lived families, however, consistently showed higher concentrations of CtBP2 in their blood. In contrast, individuals with advanced diabetes complications had notably lower levels. These results suggest that measuring CtBP2 in the blood could serve as a useful biomarker for assessing both biological aging and overall health.

The researchers believe their discovery could pave the way for new ways to monitor and promote healthy aging. By using CtBP2 as an indicator, doctors and scientists may one day be able to estimate a person’s aging status and develop personalized health strategies. Future research could also explore how to safely boost CtBP2 secretion in the bloodstream to slow age-related decline and improve overall well-being.

This research 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.)