Aging is the main risk factor for Alzheimer’s disease (AD), a prevalent and devastating neurodegenerative pathology with no effective cure. Research efforts aimed at understanding the link between pathological aging (senescence) and AD are crucial for developing pharmacological therapeutic strategies. Mitochondrial dysfunction and mitophagy defects are observed during senescence and AD, and studies suggest that they might lead to Aβ accumulation. Our goal in this project was to explore if a reduced removal of dysfunctional mitochondria during aging is a key contributor to amyloid pathology and neurodegeneration in AD.Since telomere attrition is a known trigger of cellular senescence, we used a telomerase-deficient mouse model, the Terc-/- mouse, as a model of pathological aging. Primary cultures and brain tissue from Terc-/- mice were evaluated for mitochondrial function and mitophagy alterations. To investigate the link between amyloid-β (Aβ) pathology and mitochondrial dysfunction, we crossed the Terc-/- mice with an AD-related amyloid mouse model and we explored the interplay between mitophagy alterations and Aβ accumulation in disease-vulnerable regions.We evidenced the presence of mitochondria displaying several features of dysfunction in senescent neurons. The senescence context was shown to increase Aβ levels in specific brain regions of an AD mouse model and we suggest that mitochondrial dysfunction and altered mitophagy could be key underlying mechanisms for this phenomenon.Overall, our results indicate that mitochondria become dysfunctional and accumulate during telomere-induced senescence, which could have important implications for amyloid-induced neuropathology.