A forest ages in different ways. In one spot the trees thin out gradually, as if they have grown tired of growing, while in another they cling stubbornly to life, spending their strength repairing damaged branches. The aging of the brain's cortex looks much the same when you view it through the lens of thousands of MRI scans.
Researchers took scans from 952 healthy people and divided the cortex into 148 regions. For each region they measured eight shape features: thickness, area, volume, curvature. They then built maps of how these features change together across three large brain networks: the default mode network, the attention network and the visual network.
It turned out that people fall into two groups. In the first, the changes resemble ordinary decline: cortical regions responsible for metabolism and immunity change in a coordinated way. In the second, the changes look like an attempt to compensate for damage: genes that help cells cope with stress, repair DNA and clear out broken proteins become active. The second group was on average 4.5 years older, but this difference was not statistically significant.
The link between brain shape and gene activity proved stronger in the left hemisphere: there genes explained 24% of the variation, while in the right hemisphere only 10%. This hints that the left hemisphere is more sensitive to the molecular processes of aging. When the researchers compared both groups with people who already have cognitive impairment, the first group turned out to resemble them more closely. That means "ordinary" aging may be closer to disease than "compensatory" aging.
Previously it was unclear how the molecular mechanisms of aging are reflected in the organization of cortical networks, and whether distinct paths of aging could be identified. Now it has become clear that there are at least two such paths. One leads to familiar decline, the other to stubborn adaptation. The forest does not age uniformly, and that changes how we think about what counts as normal.
For now this is pure knowledge, but it could become the basis for biomarkers that distinguish normal aging from pathological aging at early stages. If we learn to see which path a given person's brain is taking, we will be able to tailor individual ways of supporting it.
The mean age difference between subtypes was 4.5 years, but it was not statistically significant. At the same time, age explained about 93% of the accuracy in classifying subtypes, which highlights the complex relationship between chronological and biological aging.
The idea of different paths of brain aging echoes Greg Egan's novel Permutation City, where people can choose different trajectories of existence. Here, nature seems to offer two scenarios: one leads to decline, the other to adaptation.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.