Interferon-responsive oligodendrocytes emerge during white matter aging in killifish
The newly identified cellular state mirrors disease-associated glia in mammals and arises before overt signs of neurodegeneration appear.
In a new preprint, researchers investigated white matter aging in the killifish optic nerve using transcriptomic, histological, and ultrastructural analyses. The killifish tissue mimicked key features of mammalian white matter aging, showing depleted oligodendroglial progenitor cells, metabolic dysfunction, and reduced myelin thickness. During aging, the researchers observed the emergence of a distinct interferon-responsive oligodendroglial state. This cell state was marked by interferon response and antigen presentation programs. These molecular programs closely resemble pathology-associated oligodendroglia previously identified in mouse models of central nervous system disease. The authors found that this altered cellular state develops before overt neurodegeneration occurs.
Why it matters
The findings show that oligodendroglial dysfunction is an evolutionarily conserved feature of white matter aging. This shared biology suggests a cellular mechanism connecting normal brain aging to neurodegenerative diseases.
Caveats
The study was conducted in killifish optic nerves, and its findings have been reported in a preprint that has not yet undergone peer review.
The paper
An evolutionarily conserved interferon-responsive oligodendroglial state emerges during white matter aging
Serneels P, De Schutter JD, Masin L et al.
bioRxiv · 25 Sep 2026 · Preprint, not yet peer-reviewed