I always assumed an aging brain could never have too much myelin, so when I read that the people whose thinking slipped fastest in old age had thicker myelin, my first guess was that someone had flipped a sign in a spreadsheet. Myelin is the fatty insulation wrapped around nerve fibers. It keeps signals quick, and multiple sclerosis is, at bottom, an immune attack that strips it away. More of it had to be good. Right?
Nobody had flipped anything. The result comes from a Nature Medicine paper by Véronique Miron’s group at the UK Dementia Research Institute in Edinburgh, first-authored by Georgina Craig, and it recasts the oligodendrocyte, the cell that manufactures myelin and wraps it around axons, as a possible culprit in age-related decline instead of a dependable helper. “We have always considered oligodendrocytes as purely beneficial,” Craig said in the University of Edinburgh announcement when the paper went online in August, and ScienceDaily ran the story again this month as it landed in the journal’s October issue.
The people behind it are the Lothian Birth Cohort 1936, Scots whose thinking was first measured in childhood. Of 1,091 members, 866 completed memory, processing-speed and spatial-skills testing between ages 70 and 82, according to the university. Then came the detail in News-Medical’s walkthrough of the methods that stopped me cold: 865 of those 866 people declined. You and I aren’t going to dodge this. What differs from one person to the next is the speed, and speed is what the study measured.
From participants who later died, the team took tissue from the corpus callosum, the thick band of white matter joining the brain’s two halves. They measured individual axons and their myelin under an electron microscope, and used single-nucleus RNA sequencing to read which genes each oligodendrocyte had switched on. As the paper’s abstract puts it, worse cognitive trajectories “unexpectedly associate with smaller myelinated axon size.” Faster decliners had fewer large nerve fibers, and around the big fibers that remained (anything over one micrometer across) the myelin was thicker and more decompacted, its tightly stacked layers coming loose. Their white matter also held more oligodendrocytes, and a smaller share of those cells expressed a protein called NRF2. Smaller axons went along with more advanced Braak stages too, the scale pathologists use to track how far Alzheimer’s tau tangles have spread. One caution belongs right beside all of this: the tissue came from what News-Medical describes as “small subsets of participants,” from a single brain region, in a “predominantly white European Scottish cohort.”
A stress switch that went quiet
NRF2 is a master switch for a cell’s stress defenses. When oxidative strain builds, it flips on a battery of antioxidant and detox genes, and oligodendrocytes lean on that protection harder than most cells because building and maintaining myelin burns through enormous amounts of fuel and oxygen. In the faster decliners, one group of oligodendrocytes had cranked up genes tied to oxidative stress and DNA damage, while another turned down genes that keep mitochondria running and help the cells mature.
So wait, why would a cell pile extra insulation onto the big wires while the wiring overall gets smaller? Here’s how I picture it, and it’s my picture, not something the paper proved: a cell that has lost its stress brakes keeps churning out wrapping, thicker and sloppier, that the nerve fiber can’t actually use. News-Medical’s summary of the paper is more careful, saying only that oligodendrocytes “may become actively detrimental with age.”
To push past correlation, the team deleted the NRF2 gene (Nfe2l2) only in the oligodendrocytes of mice at six months old, then studied the animals between 12 and 15 months. The knockouts developed the human pattern, smaller axons wrapped in thicker myelin, though without the extra oligodendrocytes. Their cognitive result needs a careful read. Aged mice normally get better at the Morris water maze with repetition, and the knockouts still improved, just less. That’s a flatter learning curve, not a memory collapse.
Then there’s the sentence that bothers me most as someone who covers women’s health: “Female knockout mice were excluded from the cognitive analysis because they showed altered anxiety-like behavior.” The causal evidence that this pathway shapes thinking comes from male mice, which means the animals standing in for aging women were dropped from the one test that matters most.
The drug pitch arrives early
The study ran on public money, from the UK Medical Research Council and the Canadian Institutes of Health Research. Even so, the university’s announcement gets to repurposing fast. It says “the NRF2 pathway is already targeted by drugs including one that treats multiple sclerosis (MS),” and that “previous research has shown that activating NRF2 can improve cognitive function in people with MS.” It names neither the drug nor the research. The NRF2-activating MS drugs on the market are the fumarates, whose flagship is Biogen’s Tecfidera (dimethyl fumarate), so that’s the one I went looking for. The cognition study I found, Amato and colleagues in Neurological Sciences, followed 217 relapsing-remitting MS patients on the drug for two years with no control group, and MDedge reported that Biogen funded it. Of the 49 patients who started out cognitively impaired, only 34 had two-year data, and 15 of those still got worse. Without a comparison arm, nobody can say whether the drug slowed anything or whether those patients would have fared the same without it.
Before anyone pictures this pill for healthy 75-year-olds, look at its record. In November 2014 the FDA warned that a 54-year-old woman who had taken Tecfidera for more than four years developed PML, a rare brain infection caused by the JC virus, and died. Her lymphocyte count had been low. The agency told doctors to stop the drug at the first sign of PML. Repurposing an immune-modulating drug for ordinary aging should face a very high bar, and a water-maze result in male mice doesn’t come close to clearing it.
What about broccoli?
NRF2 is also what sulforaphane switches on. That compound forms from glucoraphanin, found in broccoli and especially broccoli sprouts, when a plant enzyme or your gut bacteria break it down, so the wellness question deserves a straight answer. The closest human test I could find is Nouchi and colleagues’ trial in Frontiers in Aging Neuroscience, in which 144 healthy Japanese adults aged 60 to 80 took capsules delivering 30 mg of glucoraphanin a day, or a placebo, for 12 weeks. On a symbol-search test of processing speed, the trial’s primary outcome, scores rose 1.99 points in the supplement group versus 1.29 on placebo, a between-group difference that held after adjustment, and mood scores improved too. Working memory didn’t budge, and neither did HO-1 and GST, the blood enzymes NRF2 is supposed to switch on.
| Group | Value (points) |
|---|---|
| Glucoraphanin capsules | 1.99 |
| Placebo | 1.29 |
That’s a gap of 0.70 points on one test. Kagome funded the trial and supplied the capsules, and three of the authors were full-time Kagome employees.
Neither that trial nor the Edinburgh paper shows that sulforaphane, or any fumarate, reaches the oligodendrocytes of an aging corpus callosum. What Edinburgh did hand us is a sharper question than “more myelin, good.” If the cells wrapping our nerves start overbuilding once their stress defenses fade, the experiment I’d want is an NRF2 activator given to older adults with white-matter imaging and cognition both tracked, run by someone with no capsule to sell.
Until that exists, I’ll keep broccoli sprouts on my plate because they’re cheap food, but I won’t buy a capsule marketed for “white matter,” and I wouldn’t ask a doctor for an MS drug on the strength of this paper.
Sources
- Craig, Miron et al., “Oligodendrocyte dysfunction in human age-related cognitive decline,” Nature Medicine (2026)
- UK Dementia Research Institute: publication record and abstract
- University of Edinburgh announcement
- News-Medical’s walkthrough of the methods
- ScienceDaily: “Brain cells meant to protect us may be fueling cognitive decline” (October 2026)
- Nouchi and colleagues’ trial in Frontiers in Aging Neuroscience
- Amato and colleagues in Neurological Sciences
- MDedge: Biogen-funded single-arm dimethyl fumarate cognition study
- HCPLive: FDA drug safety communication on PML death with Tecfidera (2014)