Fig. 4. Boosting mitophagy ameliorates age-associated neurological decline.

a Urolithin A (UA, 2.3 mg/kg/day during 8 weeks i.p.) treatment of young and old C57BL/6J mito-QC mice: experimental design and readouts (top) and UPLC-ESI-QTOF-MS quantification of the UA levels in perfused brain and plasma (bottom) (n = 2–3 mice). Created with BioRender.com. b Mitophagy analysis in whole eye cryosections from young and old mice. Representative images (left) and corresponding quantification (right). Dotted line indicates mean in respective vehicle-treated controls (n = 5–7 mice). c Mitophagy analysis in RPE flatmounts from young and old mice. Dotted line indicates mean in respective vehicle-treated controls (n = 5–7 mice). d Hindlimb clasping score in young and old mice treated with vehicle or UA (n = 5–7 mice). A lower score indicates greater neurological functionality. e Discrimination index in the novel object recognition (NOR) test for young and old mice treated with vehicle or UA (n = 5–7 mice). f Electroretinogram (ERG) assessment of visual function in scotopic (dark) conditions in young and old mice treated with vehicle or UA (n = 5–7 mice). g Quantification of b-wave amplitude (μV) at 0.01 cd·s·m⁻² from f (n = 5–7 mice). h Synaptic integrity analysis using immunostaining for pre- (CtBP2, cyan) and post- (mGluR6, red) synaptic terminal markers in young and old mouse retinas: representative images and corresponding quantification (n = 5–7 mice). i Detection of lipid peroxidation aggregates using anti-4-HNE immunostaining: representative images and quantification (n = 5–7 mice). j Retinal morphometric assessment by optical coherence tomography (OCT): representative images (n = 5–7 mice). Scale bars, 25 μm (b, c, i) and 15 μm (h). All data are expressed as the mean ± s.e.m. Dots represent individual mice. P values were calculated using a two-tailed Student’s t test (b, c) or 2-way ANOVA with Tukey’s post-hoc test (d, e, g, h, i). Source data are provided as a Source Data file.