Iron and the ageing brain

How can we improve brain health as we get older? This is at the forefront of research by a team at the Florey examining brain ageing with the help of C.elegans roundworms. They have discovered that the answer might lie in a commonly-found mineral – iron.

C. elegans roundworms are an ideal research model for studying ageing as their entire genome is known and easily studied by scientists. These animals grow from a single cell into an adult worm in just three days and die of old age in two weeks.

“Iron plays a crucial role in cell self-defence. When cells become infected or cancerous, they can metabolise iron stores and ‘self-destruct’ through a process known as ferroptosis. As cells age, we believe ferroptosis can be triggered unnecessarily and contribute to age-related diseases such as Alzheimer’s disease and stroke,” said Professor Ashley Bush, Co-head of The Florey’s Dementia Research theme.

In their recent studies, Associate Professor Gawain McColl, Dr Nicole Jenkins and Professor Bush showed that by blocking ferroptosis and lowering iron levels using two different approaches they could improve brain health in ageing C.elegans animal models.

C. elegans roundworms

“What we found was that the animals not only lived longer, but they were also fitter for longer. We saw reduced frailty in the animals and most impressively, we were able to double the length of their typical lifespan,” explained Associate Professor McColl, Head of The Florey’s Molecular Gerontology Laboratory who led the study.

“This research opens new prospects for healthy ageing and treatment approaches for a range of neurodegenerative diseases. Our profound understanding of what happens to cells during biological ageing means that we are now able to explore ways to reduce damage and, in turn, decrease the risk of age-related disease.”

The team are also examining ferroptosis-blocking therapies in the hope that early therapeutic intervention may hold benefits in reducing the prevalence of certain neurodegenerative diseases. Drawing on the outcomes of the work in C.elegans, the team are now trialling a potential therapy which could treat iron overload in Alzheimer’s disease.

“It’s an exciting time in medical research,” said Dr Nicole Jenkins, Senior Research Officer in the Molecular Gerontology Lab. “To understand processes as complex as ageing and neurodegeneration requires truly multidisciplinary research and I feel fortunate to work with world class scientists at The Florey where such research is possible.”

Associate Professor Gawain McColl, Head of the Molecular Gerontology Laboratory

Gawain recently presented at The Florey public lecture on iron and the ageing brain. The Currency of Aging can be viewed here.