A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults

Abstract

The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS accumulation by depletion of Cu/Zn-SOD (SOD1) or Mn-SOD (SOD2) influenced age-related impairment of the nervous system and muscles in Drosophila. We confirmed the efficient depletion of Sod1 and Sod2 through RNAi and ROS accumulation by monitoring of ROS-inducible gene expression. Both RNAi flies displayed accelerated impairment of locomotor activity with age and shortened lifespan. Similarly, adults with nervous system-specific depletion of Sod1 or Sod2 also showed reduced lifespan. We then found an accelerated loss of dopaminergic neurons in the flies with suppressed SOD expression. A half-dose reduction of three pro-apoptotic genes resulted in a significant suppression of the neuronal loss, suggesting that apoptosis was involved in the neuronal loss caused by SOD silencing. In addition, depletion of Sod1 or Sod2 in musculature is also associated with enhancement of age-related locomotion impairment. In indirect flight muscles from SOD-depleted adults, abnormal protein aggregates containing poly-ubiquitin accumulated at an early adult stage and continued to increase as the flies aged. Most of these protein aggregates were observed between myofibril layers. Moreover, immuno-electron microscopy indicated that the aggregates were predominantly localized in damaged mitochondria. These findings suggest that muscular and neuronal ROS accumulation may have a significant effect on age-dependent impairment of the Drosophila adults.

Loss of BOSS Causes Shortened Lifespan with Mitochondrial Dysfunction in Drosophila

“…SOD1 localizes to the cytoplasm, SOD2 to the in the mitochondrial matrix, and SOD3 to the extracellular space. Loss of either SOD1 or SOD2 causes early lethality in flies and mice [30, 31], whereas ubiquitous overexpression of either SOD1 or SOD2 extends lifespan [32–36]. This is in line with our findings that boss mutant flies have increased oxidative stress levels and increased sensitivity to oxidative stress.…”

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

“…Seminal experiments showed that genetic manipulation of catalase and superoxide dismutase protein SOD could alter lifespan in the fly [32, 35]. The systemic and cell specific effects of catalase and SOD in the fly are not yet fully clear and adult muscle specific expression of these proteins has not been assayed in homogenized genetic background conditions.…”

Mitochondrial responsibility in ageing process: innocent, suspect or guilty

“…However, other studies support the deleterious role of ROS on aging. Very recent studies performed in Drosophila showed that depletion of SOD1 and SOD2 in muscle and nervous system produced ROS accumulation, impairment of locomotive activity and shortened lifespan (Oka et al 2015). Then, the role of ROS in longevity in Drosophila is also not clear and different studies show controverted results.…”