Advantages
- Induction by Anti-aging Compounds: The exosome secretion of CtBP2 has been confirmed to be induced in response to stimuli with anti-aging properties, such as metformin, resveratrol, and hydrogen sulfide (H₂S).
- Correlation with Healthy Longevity and Aging: Blood CtBP2 concentration is significantly higher in relatives of long-living families, while it significantly decreases with age. This suggests its potential as a metabolic marker that directly reflects healthy longevity and the degree of aging.
- Correlation with Lifestyle (Smoking): Blood CtBP2 concentration has been confirmed to be significantly lower in smokers, particularly in men, compared to non-smokers.
Technology Overview & Background
CtBP2 (C-terminal Binding Protein 2) is a metabolic sensor molecule that regulates the expression of metabolism-related genes by sensing intracellular metabolites like NADH and fatty acyl-CoA and interacting with transcription factors. When CtBP2 is associated with NADH, reflecting the cell’s energy state, it forms a dimer and functions as a transcriptional repressor. However, when excess fatty acyl-CoA binds to CtBP2, such as during obesity, this dimeric structure is disrupted, leading to its dysfunction. As a result, the repression of genes involved in metabolic syndrome is liberated, which has been reported to cause a breakdown in metabolic regulation.
Recently, inventors discovered that CtBP2 becomes a dimeric form and is secreted into the bloodstream in response to stimuli from aging-related metabolites such as metformin and resveratrol. Furthermore, upon measuring human blood CtBP2 concentrations, they found that levels are significantly higher in long-living families and gradually decrease with age. It was also confirmed that smokers tend to have lower blood CtBP2 concentrations than non-smokers. As the administration of CtBP2-containing exosomes to mice confirmed a life-extending effect, CtBP2 is expected to be utilized as a biomarker that reflects the metabolic health status indicative of aging.
Data
- Treating cells with compounds having anti-aging properties (e.g., metformin, resveratrol) resulted in an increased secretion of CtBP2-containing exosomes.
- Measurement of plasma CtBP2 concentration in humans aged 30 to 69 showed higher levels in long-living families (A, B).
- An investigation into the relationship between smoking habits and blood CtBP2 concentration showed that CtBP2 concentration decreased stepwise according to smoking history (C).
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Publication(s)
- Sekiya, M et al., Cell Reports. Vol. 42, Issue 8, 112914 August 29(2023)
DOI: https://doi.org/10.1016/j.celrep.2023.112914 - Sekiya, M et al., Nature Communications. 12:6315 (2021)
DOI: https://doi.org/10.1038/s41467-021-26638-5 - Nature Aging (2025) in press
Patent(s)
JP Patent No. 6894119
Additional pending (unpublished) patents exist.
Principal Investigator & Academic Institution
Dr. Motohiro Sekiya (University of Tsukuba)
Expectations
The University of Tsukuba is seeking joint research collaborations with companies involved in developing health foods and Foods with Function Claims (FFC) based on the concepts of anti-aging and metabolic activation, using blood CtBP2 concentration as an indicator. Specifically, we are interested in jointly conducting the screening of new materials and the functional evaluation of products by applying this marker as an objective evaluation index for product development. We are prepared to disclose detailed, unpublished data under a Non-Disclosure Agreement (NDA) and are available for direct meetings with the inventor to discuss specific collaboration plans.
Project ID:WL-05166b