Senescent glia link mitochondrial dysfunction and lipid accumulation

Senescent glia link mitochondrial dysfunction and lipid accumulation

5 June 2024 | China N. Byrns12, Alexandra E. Perlegos5,3, Karl N. Miller4, Zhecheng Jin2, Faith R. Carranza2, Palak Manchandra5, Connor H. Beveridge5, Caitlin E. Randolph5, V. Sai Chaluvadi13, Shirley L. Zhang4, Ananth R. Srinivasan2, F. C. Bennett78, Amita Sehgal6, Peter D. Adams4, Gaurav Chopra8,9,10,11,12 & Nancy M. Bonini2,3
The study investigates the role of senescent glia in aging and age-related diseases, focusing on *Drosophila*. Senescent glia, characterized by Activator protein 1 (API) activity, are found to appear in response to neuronal mitochondrial dysfunction and promote lipid accumulation in non-senescent glia. In *Drosophila*, these senescent glia accumulate in a stereotyped manner, coinciding with neuronal decline. Targeting API activity in senescent glia mitigates senescence biomarkers, extends lifespan, and improves health span, but also increases oxidative damage and impairs neuronal mitochondrial function. The findings suggest that senescent glia link mitochondrial dysfunction and lipid accumulation, which are key phenomena in aging. In mammalian cells, API activity in senescent cells promotes lipid droplet formation in non-senescent cells, highlighting the cross-talk between senescent and non-senescent cells in aging tissues.The study investigates the role of senescent glia in aging and age-related diseases, focusing on *Drosophila*. Senescent glia, characterized by Activator protein 1 (API) activity, are found to appear in response to neuronal mitochondrial dysfunction and promote lipid accumulation in non-senescent glia. In *Drosophila*, these senescent glia accumulate in a stereotyped manner, coinciding with neuronal decline. Targeting API activity in senescent glia mitigates senescence biomarkers, extends lifespan, and improves health span, but also increases oxidative damage and impairs neuronal mitochondrial function. The findings suggest that senescent glia link mitochondrial dysfunction and lipid accumulation, which are key phenomena in aging. In mammalian cells, API activity in senescent cells promotes lipid droplet formation in non-senescent cells, highlighting the cross-talk between senescent and non-senescent cells in aging tissues.
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