Senescent glia in aging Drosophila brains are linked to mitochondrial dysfunction and lipid accumulation. This study identifies naturally occurring senescent glia in aging Drosophila brains and reveals their origin and impact. Using Activator protein 1 (AP1) activity to detect senescence, the researchers found that senescent glia appear in response to neuronal mitochondrial dysfunction. These senescent glia promote lipid accumulation in non-senescent glia, a similar effect observed in human fibroblasts. Targeting AP1 activity in senescent glia reduces senescence biomarkers, extends lifespan and health span, and prevents lipid accumulation. However, this comes at the cost of increased oxidative damage in the brain and poor neuronal mitochondrial function. The study maps the trajectory of naturally occurring senescent glia in vivo and shows that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation. Senescent glia in flies show biomarkers and traits of senescence, and their activity is marked by AP1. Loss of select mitochondrial genes in neurons can trigger glial senescence, coinciding with greater DNA damage and loss of neuronal identity. Targeting glial AP1 activity had a dose-dependent effect on animal health, with mild dampening extending lifespan and health span. The study also shows that senescent glia promote lipid accumulation in non-senescent cells, and that targeting senescent glia reduces lipid accumulation in non-senescent glia. These findings suggest that senescent cells in vivo may alter lipid storage in non-senescent cells, with implications for age-onset disease in mammals. The study highlights the role of mitochondrial dysfunction in aging and the potential of targeting senescent cells as a strategy for anti-aging therapies.Senescent glia in aging Drosophila brains are linked to mitochondrial dysfunction and lipid accumulation. This study identifies naturally occurring senescent glia in aging Drosophila brains and reveals their origin and impact. Using Activator protein 1 (AP1) activity to detect senescence, the researchers found that senescent glia appear in response to neuronal mitochondrial dysfunction. These senescent glia promote lipid accumulation in non-senescent glia, a similar effect observed in human fibroblasts. Targeting AP1 activity in senescent glia reduces senescence biomarkers, extends lifespan and health span, and prevents lipid accumulation. However, this comes at the cost of increased oxidative damage in the brain and poor neuronal mitochondrial function. The study maps the trajectory of naturally occurring senescent glia in vivo and shows that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation. Senescent glia in flies show biomarkers and traits of senescence, and their activity is marked by AP1. Loss of select mitochondrial genes in neurons can trigger glial senescence, coinciding with greater DNA damage and loss of neuronal identity. Targeting glial AP1 activity had a dose-dependent effect on animal health, with mild dampening extending lifespan and health span. The study also shows that senescent glia promote lipid accumulation in non-senescent cells, and that targeting senescent glia reduces lipid accumulation in non-senescent glia. These findings suggest that senescent cells in vivo may alter lipid storage in non-senescent cells, with implications for age-onset disease in mammals. The study highlights the role of mitochondrial dysfunction in aging and the potential of targeting senescent cells as a strategy for anti-aging therapies.