What it is
Ageing brings a slow decline of tissues and organs, and chronic low-grade inflammation ('inflammaging') is thought to drive much of it. One suspect is granzyme K (GzmK), an enzyme that rises sharply in aged memory CD8+ T cells and has been proposed as a central driver of both immune and whole-body ageing. Using mice that lack GzmK, young and aged, the authors separated those two roles. GzmK turned out to be dispensable for the main features of immune ageing, including the decline of T cell function, which persisted in its absence. Yet its deletion markedly reduced age-related tissue decline, effectively uncoupling immune ageing from organ ageing. In the kidney, the benefit came with less complement deposition (an immune-damage marker); in the liver, it came with improved function and less fibrosis, independent of complement, alongside more decorin and reduced pro-fibrotic TGF-beta signalling.
Why it matters
If a single enzyme drives organ ageing separately from immune ageing, it becomes a cleaner drug target: protect tissues without reversing immune ageing itself. Much ageing research treats inflammation and tissue decline as one tangled process. By showing that removing GzmK spares organs while leaving immune ageing untouched, the work argues the two can be pulled apart, and points to GzmK and the pathways it acts through (complement in the kidney, TGF-beta-driven fibrosis in the liver) as specific, tissue-level levers.
Every metric behind this entry is listed, with its source, under Sources and data below.
Filed underGenetics, Aging, and Longevity in Model Organisms, Telomeres, Telomerase, and Senescence, T-cell and B-cell Immunology