Aging is a systemic process that affects the entire body. Visible external signs of aging usually correspond to evidence of equivalent aging in the functioning of the internal organs. This indicates that skin cells age in tandem with other cells throughout the body, suggesting a mechanism whereby aging in one part of the body spreads systemically.
The Tsukuba research group began focusing on CtBP2 while working to elucidate the mechanisms responsible for obesity. This sensor molecule is known to respond to metabolism, and its activity has previously been reported to decrease in individuals with obesity, leading to metabolic syndrome. Furthermore, the activation of CtBP2 has demonstrated therapeutic effects.
In their detailed study of the molecular mechanisms of CtBP2, now published in Nature Aging, they found that this molecule, which was previously thought to work inside the cell, is secreted extracellularly when activated. They found that activation improves systemic metabolism and that disruption of this process leads to aging and an increase in health problems. This is in concordance with the simultaneous nature of the aging process throughout the whole body.
Upon establishing a method to measure CtBP2 levels in blood, the team found that these levels decrease with age and that individuals from long-lived families have higher blood concentrations of CtBP2. Furthermore, diabetic patients with advanced complications were found to exhibit lower blood CtBP2 levels. This suggests that blood concentrations of CtBP2 could serve as an indicator with which to estimate the degree of aging and overall health status.
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.
More information:
Motohiro Sekiya et al, The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan, Nature Aging (2025). DOI: 10.1038/s43587-025-00973-4
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