Scientists and clinicians have long sought biomarkers that can accurately measure a person's biological age, and the mechanisms that drive aging. In aging, the function of the body breaks down over time. This deterioration is often accompanied by various age-related diseases. Many processes have been linked to aging, such as cellular senescence, in which cells stop dividing; or epigenetic changes that occur in the genome, for just a couple of examples. Chronic inflammation is also closely connected to aging.
Reported in Nature Communications, scientists have now found that a gene called EDA2R (ectodysplasin A2 receptor) is overactive in diseases of accelerated aging. The overexpression of EDA2R was shown to trigger a powerful inflammatory response in animal models and mimicked some symptoms of age-related sarcopenia. Sarcopenia, or muscle degeneration, is one of many age-related diseases that are also linked to inflammation, such as cardiovascular disorders, diabetes, or some neurodenegerative diseases.
Normally, EDA2R binds to a protein called EDA-A2; it plays a role in inflammation, and a programmed pathway that leads to cell death, known as apoptosis.
In this work, the researchers found a significant link between the expression of EDA2R and aging by analyzing information about the gene in the Genotype-Tissue Expression database. This showed that the expression of EDA2R was linked to aging in different human tissues and organs.
The investigators also validated this link in animal models, and confirmed that EDA2R activity was related to accelerated aging, inflammation, and vascular dysfunction, which has also been previously associated with aging.
In cell culture models, the overexpression of EDA2R activated inflammatory signals, and triggered changes in muscle cells that are connected to sarcopenia. But when the expression of EDA2R was reduced, these symptoms were ameliorated.
This work has not only suggested that EDA2R activity is an aging biomarker, but that it may also be a driver of aging.
Additional research showed that in over 5,000 human blood samples, there was an association between the expression of EDA2R and systemic inflammation.
"These findings suggest that the EDA2R/EDA-A2 axis may play a pivotal role in mediating age-related inflammatory and degenerative processes across tissues," said penultimate study author Dr. Ildus Ahmetov, a geneticist at Liverpool John Moores University.
"Targeting EDA2R could open new therapeutic avenues for managing aging-related conditions, including sarcopenia, cardiovascular disease, neurodegeneration, and metabolic disorders. Our work has laid a strong foundation for future research aimed at developing interventions to modulate EDA2R signaling and reduce the impact of aging."
Sources: Liverpool John Moores University, Nature Communications
