Sodium arsenite accelerates aging of Caenorhabditis elegans parents and offspring through the insulin signaling pathway, oxidative stress, and autophagy.

Arsenic is a naturally occurring metalloid, and its pollution poses a global threat to humanity. Studies have shown that arsenic exposure accelerates aging, but the effects and mechanisms of sodium arsenite exposure on aging across both parental and offspring remain unclear. In this study, we investigated the effects of sodium arsenite on lifespan, locomotion, heat tolerance, antioxidant defense systems, autophagy, and the insulin/IGF-1 signaling (IIS) pathway in Caenorhabditis elegans (C. elegans). Initially, exposure from the L1 to L4 larval stage to 100 μM or 200 μM sodium arsenite significantly shortened the lifespan of C. elegans. Sodium arsenite also reduced body length, body width, head-swing frequency, and heat-stress resistance. It also reduced superoxide dismutase (SOD) activity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation in C. elegans parents and offspring. qRT-PCR analysis showed that sodium arsenite exposure activated the IIS pathway in C. elegans parents and offspring by upregulating the upstream genes age-1 and daf-2 and downregulating the downstream transcription factor daf-16. Concurrently, it reduced the mRNA levels of bec-1, lgg-1, and sod-3, indicating impaired autophagy and reduced DAF-16 activity. Furthermore, sodium arsenite exposure diminished the fluorescence intensity of LGG-1::GFP in the DA2123 strain and SOD-3::GFP in the CF1553 strain across both generations, consistent with the qRT-PCR results. To further investigate the role of autophagy, we treated worms with rapamycin, which alleviated the pro-aging effects of arsenite in both generations. Therefore, our results show that sodium arsenite exposure accelerates aging in both parental and offspring C. elegans, a process linked to the IIS pathway, oxidative stress, and autophagy.