How the Aging Spleen Shapes Immune Decline

A recent Nature Aging study from the lab of Prof. Ron Harel reveals that age-related immune dysfunction is driven not only by intrinsic T cell aging, but also by changes in the tissue microenvironment. The researchers show that the aged spleen accumulates toxic heme and iron, creating a hostile niche that accelerates T cell dysfunction. To survive this environment, T cells limit intracellular iron and become resistant to ferroptosis—but at the cost of impaired activation and proliferation. Importantly, iron supplementation restored antigen-specific T cell responses in aged mice, highlighting iron metabolism as a key regulator of immune aging and a potential target for improving immunity in older adults.