University of Tsukuba researchers report that CtBP2, a metabolic sensor protein detected in the bloodstream, tracks with age and health status in people—declining with age, remaining higher in members of long‑lived families, and falling in those with advanced diabetic complications.
Scientists at the University of Tsukuba have linked a blood‑circulating form of the protein CtBP2 to systemic metabolic regulation and indicators of healthy aging. In work published October 8, 2025, in Nature Aging, the team describes developing a blood assay for CtBP2 and reports patterns that align with aging and disease risk.
CtBP2 has been studied as a metabolite‑sensing protein involved in obesity and metabolic control. Prior research has associated lower CtBP2 activity with obesity and metabolic syndrome, while boosting CtBP2 activity has shown beneficial metabolic effects in experimental settings. In the new study, the authors report that CtBP2—previously thought to act only inside cells—is secreted and detectable in blood when activated, supporting the view that aging and metabolism are coordinated across tissues rather than occurring in isolation.
Using their blood test, the researchers found that CtBP2 concentrations tend to decline with age. Levels were higher among individuals from long‑lived families and lower in people with advanced diabetic complications. The team says these patterns suggest CtBP2 could serve as a biomarker for biological aging and overall health status, though clinical validation will be needed before any test is used in routine care.
The article, led by Motohiro Sekiya and colleagues, appears in Nature Aging (DOI: 10.1038/s43587-025-00973-4). The work was supported by the Japan Society for the Promotion of Science (grants 20K08855 and 23K18270 to M.S.), the Japan Agency for Medical Research and Development (JP18gm5910007, JP25gm6710004, JP22ek0210175), and foundations including the Takeda Science Foundation, Ono Medical Research Foundation, Manpei Suzuki Diabetes Foundation, and Japan Diabetes Foundation.
What comes next, according to the authors, is to validate CtBP2 as a clinical biomarker and to explore whether safely enhancing its secretion could help maintain metabolic health with age. Any such intervention would require further studies to establish efficacy and safety.
