Granzyme K drives age-related damage in the heart, liver, and kidneys, according to research published in Immunity.
The study identifies a protein produced by immune cells that links to signs of ageing in vital organs, opening potential new avenues for age-related treatments.
Granzyme K levels rise with age in both mice and humans. Until now, its precise role in driving age-related organ damage remained unclear.
“We know that as we get older, our organs undergo changes that can make us more susceptible to diseases, including heart and kidney disease,” said Professor Nicole La Gruta, senior researcher at the Monash Biomedicine Discovery Institute.
“What we’ve discovered is that Granzyme K plays an important role in driving some of that damage,” La Gruta said.
Researchers utilized preclinical mouse models to compare older mice lacking Granzyme K with mice that retained the protein. Mice without the protein showed reduced signs of organ ageing, while their immune systems continued to age normally.
The findings challenge the assumption that organ and immune ageing are inextricably linked. Researchers observed improved heart function and reduced fibrosis, or organ scarring, in mice lacking Granzyme K.
“What’s particularly exciting is that mice without this protein showed reduced signs of organ ageing, even though their immune systems continued to age normally,” La Gruta said.
The same mice also showed reduced signs of age-related damage in their liver and kidneys. When examining human datasets, the research team found elevated levels of Granzyme K in patients with inflammatory and fibrotic diseases such as heart failure and lupus nephritis.
Researchers are now investigating ways to selectively block Granzyme K later in life to see if it provides similar organ protection. Because the test mice lived their entire lives without the protein, determining the effects of blocking it later remains a key next step.
“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 required to determine whether the same benefits can 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,” La Gruta said.
What is Granzyme K?
Granzyme K is a protein produced by immune cells whose levels increase significantly with age in both mice and humans.
Which human diseases show elevated Granzyme K?
Human datasets show elevated levels of the protein in patients with inflammatory and fibrotic diseases, including lupus nephritis and heart failure.
Where was the research published?
The findings were published in the journal Immunity by researchers at Monash University.