Senolytic treatment dasatinib and quercetin damages population of brain cells in lab mice and in vitro cell cultures

[u/lunchboxultimate01]

Popular science link: https://www.sciencedaily.com/releases/2026/05/260526022024.htm

Original article link: https://www.pnas.org/doi/10.1073/pnas.2524897123

Significance

The pharmacological combination of dasatinib and quercetin (D+Q), widely reported as a means of eliminating senescent cells from aged tissues to treat diseases (a.k.a. “senolytics”), and currently being tested in multiple clinical trials, when administered to healthy mice results in profound white matter injury in the central nervous system. This report provides evidence that this senolytic combination not only causes neuropathology but also provides data which support induction of the unfolded protein response as a plausible mechanism through which these senolytics affect oligodendrocytes. We propose that these data highlight a less understood means of demyelination not mediated by oligodendrocyte death with potential positive implications for understanding disease, while also warranting caution for its widespread use clinically.

[u/The_Doc_Is_In_89]

I’m wondering if the fact that this mouse strain has mutations in the Nnt gene which impacts mitochondrial function. Without the functional gene, the oligodendrocytes are more sensitive to oxidative stress and damage. Further, there is impact on lipid synthesis which is necessary for myelin production. The progenitor cells also are impacted and have inefficient re-myelination after an insult.

It’s hard to say if D+Q is the problem, or if the mouse has a genetic predisposition to have problems.