Monash scientists identify protein driving age-related damage in heart, liver and kidneys

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A protein made by the immune system drives age-related damage in the heart, liver and kidneys, researchers at Monash University have found — and removing it in mice left those organs in markedly better shape.

The protein is Granzyme K, produced by immune cells, whose levels rise sharply with age in both mice and people. In the study, published in the journal Immunity, older mice engineered to lack Granzyme K showed better heart function and less scarring in the heart, liver and kidneys than ordinary mice of the same age, even though their immune systems aged normally. The team also found raised levels of the protein in human patients with heart failure and with lupus nephritis, a kidney disease.

The work was led by Professor Nicole La Gruta at the Monash Biomedicine Discovery Institute. Her team is now testing ways to block Granzyme K selectively, to see whether switching it off later in life offers the same protection the mice born without it enjoyed. She cautioned that further research is needed to establish what the protein does in people.

The mouse findings are published and peer-reviewed, and the human evidence is of a different kind: higher Granzyme K in the blood and tissues of people with inflammatory and fibrotic disease, which shows an association rather than a cause. Nothing in the paper shows that blocking the protein would help a person, and the researchers say so themselves. The result is a new target for ageing research, not a treatment.

Ageing is the largest risk factor for the diseases that fill hospitals, and most of the damage it does to organs has no treatment at all. A single protein that can be switched off, with the immune system otherwise untouched, is the kind of lead drug researchers look for — but the distance between a mouse that never had the protein and a person who might one day have it blocked is exactly what the next round of work has to cross.