Inflammation and Aging: Ties to the AP-1 Complex

A 2023 research example from Ron Korstanje and Duygu Ucar from The Jackson Laboratory

JAX researchers reveal proteins from two families are consistently activated and likely play a role in promoting chronic inflammation with age.

Our aging immune system

Researchers have long sought to understand the causes of inflammaging, the state of increased and chronic inflammation that occurs as we age. Inflammaging is considered as the culprit behind diverse aging diseases. It is characterized by increased levels of pro-inflammatory molecules in blood and tissues as well as changes in the immune system's composition and function. Considered one of the hallmarks of aging and linked to a variety of age-related diseases, including cardiovascular disease, Alzheimer's disease and cancer, it begs the question, what is contributing to this prevalent problem?

A little complex

As presented in a paper published in Aging Cell, Associate Professor Duygu Ucar, Ph.D. and fellow JAX researchers have identified a possible answer to this question by focusing on an important protein assembly called the activating protein-1 (AP-1) complex. The AP-1 complex is a key regulator of cellular responses to outside stimuli such as stress or viral infection by releasing pro-inflammatory signals. Ucar and team employed diverse -omics assays to profile multiple cell and immune tissue types to hone in on what are the most significant -omics changes occurring with age. The study used both long-living and short-living mice strains to represent healthy and unhealthy aging in humans.

Identifying an inflammation signature

The collaborative effort revealed the most significant aging signal — the activation of two gene families, Jun and Fos, in the AP-1 complex across mouse models and cell types. With age, these genes are more active resulting in an increased production of corresponding proteins when immune cells are activated. The good news is that the researchers believe the consistently activated Jun and Fos family members in the AP-1 complex can act as a biomarker for immune aging.