Researchers found that the metabolic molecule CtBP2 may indicate biological aging and health status. Higher levels correlate with longevity and better metabolism.
Aging affects every organ and tissue in the body, functioning as a unified process rather than an isolated one. The visible signs of aging on the skin often mirror similar deterioration occurring within internal organs.
This relationship indicates that when one part of the body begins to age, it can influence other systems as well, pointing to a shared biological mechanism that drives aging throughout the body.
Investigating the role of CtBP2 in metabolism and aging
The research team at the University of Tsukuba began studying CtBP2 while examining how metabolic regulation is connected to obesity. CtBP2 acts as a metabolic sensor, and prior studies have shown that its activity is reduced in people with obesity, contributing to metabolic syndrome. However, activating CtBP2 has been linked to beneficial effects on metabolic health.
Through detailed molecular analysis, the researchers discovered that CtBP2, previously thought to function only within cells, is actually secreted outside the cell when activated. They also found that activation of CtBP2 improves metabolic efficiency across the body, whereas disruption of this process promotes aging and increases health-related complications. These findings support the idea that aging progresses in a coordinated fashion across multiple organs.
The team then developed a method to measure CtBP2 levels in blood samples. Their results showed that CtBP2 levels naturally decrease with age, while individuals from long-lived families tend to maintain higher concentrations. In contrast, patients with diabetes and advanced complications had significantly lower levels. This suggests that blood CtBP2 levels could serve as a useful biomarker for evaluating biological aging and overall health status.
Toward new anti-aging and health monitoring strategies
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.
Reference: “The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan” by Motohiro Sekiya, Kenta Kainoh, Wanpei Chen, Daichi Yamazaki, Tomomi Tsuyuzaki, Yuto Kobari, Ayumi Nakata, Kenji Saito, Nao Aono-Soma, Ali Majid, Hiroshi Ohno, Takafumi Miyamoto, Takashi Matsuzaka, Rikako Nakajima, Takaaki Matsuda, Yuki Murayama, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki and Hitoshi Shimano, 8 October 2025, Nature Aging.
DOI: 10.1038/s43587-025-00973-4
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 Foundatio,n and Japan Diabetes Foundation (to M.S.).
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