The powerful role of exercise in maintaining skeletal muscle could be the key to improving health and resilience in older age, according to new research from Monash University.
Physical activity is one of the most powerful ways to combat biological ageing, which is the way our organs and tissue decline as we get older.
The new research, published today in Science Advances , has used preclinical models to uncover the key role a protein found in skeletal muscle, NOX4, plays in this process.
Physical activity and NOX4 naturally declines as we age, making it more difficult to achieve the health and anti-ageing benefits of exercise.
The research shows lower levels of NOX4 are associated with muscle wasting and frailty, while restored levels are linked to better regulated metabolism and improved muscle mass and strength.
Senior author Professor Tony Tiganis , from Monash Biomedicine Discovery Institute , said finding alternate ways to trigger the same responses in skeletal muscle could help people retain muscle mass and strength when NOX4 declines with age.
“Our findings could present a significant new target for therapies that would drastically improve life for many older people,” Professor Tiganis said.
“If we can find other ways to mimic the processes started by NOX4, we could successfully combat biological ageing and improve health span.
“So perhaps there is some truth to the old adage, ‘you are only as old as you feel’.”
This research builds on previous work by Professor Tiganis and his team , led by Monash research fellow Dr Chrysovalantou Xirouchaki , which found NOX4 acts as a signal to muscles to release oxygen-rich molecules that help cells adapt, improve energy production, reduce damage and maintain overall health.
Dr Xirouchaki said the next step would be to identify “downstream” or subsequent cellular signals triggered by NOX4 that could be replicated.
“We aim to harness naturally occurring compounds from cruciferous vegetables such as broccoli, cabbage and brussels sprouts, to restore this pathway, potentially replicating some of the health benefits of exercise during ageing,” Dr Xirouchaki said.
Read the research paper: https://doi.org/10.64898/2026.03.27.714615
Science Advances
Experimental study
Animals
A decline in skeletal muscle NOX4 abrogates adaptive homeostasis and exacerbates ageing
11-Jun-2026