Accumulation of F-actin drives brain aging and limits healthspan in Drosophila.
Abstract
The actin cytoskeleton is a key determinant of cell structure and homeostasis. However, possible tissue-specific changes to actin dynamics during aging, notably brain aging, are not understood. Here, we show that there is an age-related increase in filamentous actin (F-actin) in Drosophila brains, which is counteracted by prolongevity interventions. Critically, decreasing F-actin levels in aging neurons prevents age-onset cognitive decline and extends organismal healthspan. Mechanistically, we show that autophagy, a recycling process required for neuronal homeostasis, is disabled upon actin dysregulation in the aged brain. Remarkably, disrupting actin polymerization in aged animals with cytoskeletal drugs restores brain autophagy to youthful levels and reverses cellular hallmarks of brain aging. Finally, reducing F-actin levels in aging neurons slows brain aging and promotes healthspan in an autophagy-dependent manner. Our data identify excess actin polymerization as a hallmark of brain aging, which can be targeted to reverse brain aging phenotypes and prolong healthspan.
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Research summary
The paper addresses the accumulation of F-actin in the aging brain of Drosophila and its implications for cognitive decline and healthspan, which are directly related to the mechanisms of aging. By identifying excess actin polymerization as a hallmark of brain aging and demonstrating that targeting this process can reverse age-related phenotypes, the research contributes valuable insights into potential interventions for longevity. However, while the findings are important, they primarily focus on a specific model organism and may have limited immediate applicability to broader aging research, thus warranting a moderate impact score.
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