Finding. Take microglia away from a 21-month-old mouse with a CSF1R inhibitor and the microRNAs that live in microglia (miR-146a-5p, miR-223-3p) fall in both sexes. Everything else splits. Beganovic, Keller and colleagues show female spatial transcriptomes mostly go quiet, cell type by cell type. Males go both ways (Lzts3, Shank3, Fgfbp1 up; Ang down). Proteomics is the real dimorphism: 295 differential proteins in males, 34 in females. In males, synaptic-vesicle proteins rise and mitochondrial ATP-synthesis machinery falls, and that proteome does not follow the mRNA.
Why mitochondria are in it
Aged circuits run close to their ATP budget. If losing microglia drops ATP-synthase proteins in males only, CSF1R “cleanup” experiments in old animals are a bioenergetic intervention with a sex. The uncoupling from transcript is a warning against RNA-only reads of this model.
How to read the score
Low seventies. Real mitochondrial proteomic move, aged brain, sex. Confidence is medium: bulk protein, no respiration, PLX caveats. Not a new mitophagy pathway.
Caveats
Whose mitochondria? Residual drug effects? Do not stop a human CSF1R trial from a mouse proteome.
What to do with it
Stratify aged microglial-depletion papers by sex. If you measure OXPHOS after PLX in old males, expect a protein-level ATP-synthase drop. Pull the DEP lists before you believe the spatial RNA.