Scientists identify protein driving age-related organ damage
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Monash University researchers have identified a protein that drives age-related damage in vital organs, opening a potential new avenue for treatments that could help people stay healthier as they get older. Published in Immunity, the research revealed a link between the protein granzyme K and signs of aging in the heart, liver and kidneys.
Granzyme K is a protein produced by immune cells, with levels known to increase significantly with age in both mice and humans, but its precise role in age-related organ damage has remained unclear.
Senior researcher Professor Nicole La Gruta, from the Monash Biomedicine Discovery Institute, said the findings could provide a new way to protect vital organs from damage as we age.
"We know that as we get older, our organs undergo changes that can make us more susceptible to diseases, including heart and kidney disease," La Gruta said.
"What we've discovered is that granzyme K plays an important role in driving some of that damage.
"What's particularly exciting is that mice without this protein showed reduced signs of organ aging, even though their immune systems continued to age normally.
"This challenges the long-held assumption that organ and immune aging are inextricably linked and opens up an exciting new avenue for developing treatments that could help people maintain healthier organs for longer."
Reduced damage across three organs
The study used preclinical or mouse models, comparing older mice that did not have the protein granzyme K with those that did.
In mice lacking granzyme K, researchers observed significantly improved heart function and reduced fibrosis, a form of scarring that can affect how well the organ works.
The mice also showed reduced signs of age-related damage in their liver and kidneys.
Human links need further investigation
Upon examining human datasets, the researchers found elevated levels of granzyme K in patients with several inflammatory and fibrotic diseases, including lupus nephritis and heart failure.
But La Gruta said further research was needed to determine the role of the protein in age-related organ damage.
"This discovery is particularly significant given aging is one of the biggest risk factors for chronic conditions, including cardiovascular and kidney disease," La Gruta said.
"The damage that accumulates in our organs as we age can make us more vulnerable to developing serious health conditions later in life.
"If we can find a way to limit that damage, we may be able to help people maintain healthier organs for longer and potentially reduce their risk of age-related disease."
Testing treatment later in life
The researchers are now investigating ways to selectively block granzyme K, to determine whether targeting the protein later in life could provide similar protection.
"Because these mice have lived their entire lives without granzyme K, we now need to understand whether blocking the protein later in life could achieve similar benefits," La Gruta said.
"Further research is also needed to determine whether the same benefits could be achieved in humans.
"There's still a lot of work to do, but identifying a protein that contributes to damage across multiple organs gives us a promising new direction for research into healthier aging."
Publication details
Granzyme K is a driver of age-related tissue remodelling and functional decline independently of age-associated immune dysfunction, Immunity (2026). DOI: 10.1016/j.immuni.2026.10.013. www.cell.com/immunity/fulltext … 1074-7613(26)00440-1
Journal information: Immunity
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Healthy agingAllergy and immunology Provided by Monash University Who's behind this story?
Sadie Harley
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