Study identifies iron dysregulation in the spleen as a driver of immune aging

Researchers at the Technion – Israel Institute of Technology Faculty of Biology have identified a unique mechanism involved in the aging of the immune system – along with a framework for enhancing its function in older individuals. The study, published in Nature Aging, was led by Assistant Professor Noga Ron-Harel and doctoral student David Ezuz.

The human immune system weakens with age, partly because T cells – white blood cells responsible for identifying and destroying viruses and cancer cells – gradually lose their effectiveness.

The Technion researchers discovered that a key factor in this process is the aging of the spleen, a vital organ in the immune system. In addition to serving as the body's main reservoir of white blood cells, the spleen contains a specialized region responsible for breaking down defective red blood cells and recycling their iron-rich components. This essential process becomes less efficient with age, leading to the accumulation of iron deposits and toxic by-products in the spleen. These create an oxidative environment that damages T cells. The researchers found that even brief exposure of young T cells to an "aged spleen" impairs their immune effectiveness.

In response to this toxic environment, and in an effort to protect themselves, T cells reduce their iron uptake and sequester the iron already present within the cell in protein complexes that lower its availability. However, this protective mechanism has a downside: since available iron is essential for T-cell activation, their ability to respond is significantly weakened.

The researchers went beyond these findings and proposed a way to counter the decline in immune function – controlled iron supplementation at the time of T-cell activation. In experiments on elderly mice, this intervention improved the activation of aged T cells and enhanced the immune response of older mice to vaccination.

The research was supported by the European Research Council (ERC) under the Horizon 2020 program.