Researchers discover an aging and inflammation biomarker

Researchers discover an aging and inflammation biomarker

By
Alison Satake

December 10, 2024

Microscopy image of the gene expression of Il23r (depicted in red), which increases in aged blood at the protein level, is present in aged kidney and is associated with the senescence marker p16ink4a (shown in green). — Mayo Clinic researchers found that the gene expression of Il23r (depicted in red), which increases in aged blood at the protein level, is present in aged kidney and is associated with the senescence marker p16 (shown in green). When IL-23R signaling is overactive, it can lead to inflammation and tissue damage. Mayo Clinic researchers found that IL-23R increases with age and decreases in response to drugs that attack senescent cells.

The bloodstream is teeming with plasma proteins that can increase and decrease depending on what is happening in the body. As a result, these proteins can serve as valuable biomarkers for health.

Mayo Clinic researchers have found that a specific plasma protein, called IL-23R, increases with age. The finding reveals a connection between a cellular aging process, called senescence, and specific plasma proteins in the blood that increase with age and decrease in response to therapeutics targeting senescent cells. This new discovery is published in Nature Aging.

"Our research is the first to show that IL-23R is an aging biomarker linked to senescence. Since IL-23R influences many inflammatory conditions that can increase with age, our discovery opens new lines of investigation as to how circulating IL-23R may influence disease processes with age," says senior author Marissa Schafer, Ph.D.

IL-23R is known to alert immune cells to help fight infections through inflammation, the body's defense mechanism. However, when IL-23R is overactive, it can lead to tissue damage and drive the persistent inflammation that underlies conditions such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis.

The research team measured IL-23R levels in donated blood samples of 40 men and 40 women ranging in age from 20 to 90 years old. They found that IL-23R increased in blood circulation with age among the participants. Using a preclinical model, they showed that IL-23R is linked to markers of senescence in aged organs, particularly the kidneys.

Additionally, the researchers tested five different senotherapeutics, drugs specially designed to eliminate senescent cells. All of these drugs targeted genes or proteins that are highly expressed in senescent cells. They found the senotherapeutics reduced the amount of plasma proteins including IL-23R.

"By targeting and reducing senescent cells, we can influence the systemic landscape by decreasing inflammatory mediators that are secreted in tissues and into circulation, such as IL-23R. This suggests that IL-23R is an important aging biomarker in senescence, inflammation and organ 'cross talk' that may be useful in clinical research and practice," explains lead author Chase Carver, Ph.D.

Next steps and implications

The researchers are continuing to study how circulating IL-23R is produced, how it affects inflammatory signaling throughout the body and how it drives disease states.

They are also collaborating with others to assess if other senotherapeutic approaches or exercise reduce circulating IL-23R levels in humans.

Review the study for a complete list of authors, disclosures and funding.