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

Aging affects every part of the body, inside and out. Wrinkles and gray hair that appear on the surface often reflect similar changes occurring deep within our organs. This association suggests that aging does not occur in isolation, but rather spreads throughout the body in a coordinated manner. In other words, as one system begins to age, other systems 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 previous research has shown that its activity is reduced in people with obesity, which may contribute to metabolic syndrome. Interestingly, stimulation or activation of CtBP2 has been shown to produce therapeutic effects that improve metabolism.

Tsukuba scientists explored CtBP2 in greater depth to understand its molecular behavior. They discovered that this molecule, previously thought to work 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 throughout the body. However, when its activity is disrupted, it can lead to systemic aging and an increase in health-related problems. This finding supports the idea that aging occurs as an interconnected, body-wide process rather than as a series of isolated events.

After developing a method to measure CtBP2 levels in blood samples, researchers noticed that these levels tend to decrease with age. However, people from long-lived families consistently showed higher concentrations of CtBP2 in their blood. In contrast, individuals with advanced diabetes complications had significantly 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. 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 enhance the secretion of CtBP2 into the bloodstream to slow age-related decline and improve overall health.

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