Researchers at the Technion – Israel Institute of Technology’s Faculty of Biology have uncovered a distinctive process that contributes to immune system ageing, along with a potential strategy to strengthen immune responses in later life. The work, published in Nature Aging, was carried out by Assistant Professor Noga Ron-Harel and doctoral researcher David Ezuz.
As people grow older, their immune defences weaken, essentially because T cells—key white blood cells tasked with recognising and eliminating viruses and cancerous cells—gradually lose their capacity to function efficiently. The Technion team has shown that one of the central drivers of this decline lies in the ageing of the spleen, an organ crucial to the immune system. Beyond acting as the body’s primary reservoir of white blood cells, the spleen houses a specialised region that dismantles faulty red blood cells and recycles their iron-rich components. With age, this recycling machinery becomes increasingly ineffective, leading to the accumulation of iron deposits and harmful metabolic by-products. The result is an oxidative, damaging environment that compromises T-cell performance. Remarkably, the researchers demonstrated that even short-term exposure of young T cells to the conditions within an aged spleen is enough to blunt their effectiveness.
Faced with this stressful and toxic environment, T cells attempt to shield themselves by reducing their iron uptake and locking the iron they already contain in protective protein complexes that make it less available. While this response lessens potential oxidative damage, it comes at a high cost: readily accessible iron is indispensable for T-cell activation. By restricting it, T cells inadvertently undermine their own ability to mount a robust immune response.
Building on these observations, the researchers proposed and tested a practical way to counteract the decline in immune function associated with ageing. By providing controlled iron supplementation precisely at the time of T-cell activation, they improved the responsiveness of aged T cells. Experiments in older mice showed that this targeted intervention not only restored aspects of T-cell activation but also boosted the animals’ immune reactions to vaccination.
More information: David Ezuz et al, Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation, Nature Aging. DOI: 10.1038/s43587-025-00981-4
Journal information: Nature Aging Provided by Technion-Israel Institute of Technology
