What changes in normal human brain aging ↗
Super important work Yang et al. just published in Nature one of the first studies that actually has the power (284 brains, 1.3M nuclei) to ask what changes during 'normal' brain aging (no Alzheimer's).
Surprising: many discoveries we made 3 years ago on aging in the mouse brain seem to happen in humans, too
1⃣ It's not the neurons that seem to be most affected by age! Instead, glia and microglia (the brain's support system) change the most.
2⃣ Microglia launch ~2–3 main expression programs during normal aging: up-regulation of antigen presentation genes (HLA), launch of an interferon response (IFI44L) and induction of a 'disease-associated' program (GPNMB, SPP1) – plus the classic aging gene CD22.
3⃣ These changes don't happen uniformly across the brain. There is a 'hotspot' of aging in the white matter – the stuff beneath the neuron-dense cortex, where most of the big connections across brain regions run through.
Why do we care about any of this? Aging is the biggest risk factor for developing Alzheimer's and Parkinson's – so this helps us understand how the brain becomes vulnerable to disease.
Why care if this happens in a mouse? It suggests that some key biology of brain aging can be mechanistically studied in the lab. Diseases like Alzheimer's and Parkinson's are probably unique to humans, but the thing that drives up their risk (i.e. aging) may be somewhat conserved across species. That simplifies (a bit) the path to identify and test new drugs.
Massive kudos to Panos Roussos, Kiran Girdhar and the whole PsychAD team for delivering this big resource for the field!
