What have two landmark studies discovered about the role of your brain immune cells in ageing?
Microglia play an active role in brain ageing through fat accumulation and energy shortage, but most of the evidence still comes from animal research. Human applications do not yet exist, so if you have concerns about memory complaints, discuss them with your doctor.
Two studies show that brain immune cells, known as microglia, go off track in two ways during ageing. The first discovery concerns fat droplets: in older mice and humans, fat droplets accumulate inside microglia. These fat-laden cells clear away waste less effectively, produce more harmful substances and emit inflammation-promoting signals. Variants of the genes that drive this fat-droplet formation also occur in hereditary forms of neurodegenerative diseases, suggesting a possible link to conditions such as Alzheimer's disease.
The second discovery is about energy shortage. In older mice, increased activity of the signalling molecule prostaglandin E2, acting through a specific receptor on the cell (the EP2 receptor), causes microglia to store glucose as starch instead of using it as fuel. As a result, the cells become energy-depleted, chronic inflammation begins to smoulder, and measurable memory problems arise. When researchers blocked that EP2 receptor in old mice, cellular energy was restored, inflammation decreased and spatial memory improved.
Other research adds a third mechanism to this picture. In tissue from 437 older people, two specific microglia subtypes were found that are causally associated with Alzheimer's disease: one drives the accumulation of amyloid-beta, while the other mediates how that amyloid subsequently causes tau proteins to accumulate. Not every ageing pathway leads to Alzheimer's disease; only one of the two identified trajectories does.
In mouse models, aged, 'burnt-out' microglia with elevated levels of the p16ink4a protein (a brake on cell division) were also found to accumulate near amyloid plaques. When that protein was reduced via nanoparticle administration, mice cleared amyloid more effectively and their spatial memory recovered. This is a pre-clinical finding that has not yet been tested in humans. Finally, mouse research showed that an engineered variant of the anti-inflammatory protein IL-10, administered into the brain, stimulated the generation of new nerve cells and improved cognition, without the unwanted side effects of ordinary IL-10.
All findings are based on studies that are not further indexed (largely animal and mechanistic research, plus one study using human brain tissue from 437 individuals and one large cell atlas). No randomised clinical trial is available.
Does your brain age faster than the rest of your body?
Whether your brain ages faster than the rest of your body varies from person to person, but the consequences are significant: a biologically old brain increases the risk of Alzheimer's more than threefold. Keep an eye on your blood pressure, sleep and lifestyle, as these have the most demonstrable influence on brain ageing.
What can I do to keep my brain healthy as I age?
Combining more exercise with staying mentally active and eating a diet low in sugar and higher in omega-3 fatty acids currently gives you the best chance of a healthy brain. Spermidine and new insights into how the brain cleans itself are, for now, only interesting to follow.
Does a second language or music help protect the brain against ageing?
Speaking two or more languages daily appears to protect the brain in later life, with the strongest evidence for people who picked up a second language early in life. The available studies say nothing about music.
Does a low dose of lithium help protect the ageing brain?
There are preliminary indications that low doses of lithium may offer brain protection, but the evidence is still too thin and the risks are real enough that lithium should only be used under medical supervision.
Do your brains really shrink as you get older?
Your brain does indeed shrink with age, particularly in areas involved in memory and planning. High blood pressure accelerates that process, while exercise and cognitive effort strengthen your brain's compensatory activity.
What does smoking do to your brain as you age?
Smoking accelerates brain ageing and increases the risk of dementia. Quitting smoking is one of the best-supported steps you can take to keep your brain healthy for as long as possible.