Paroxetine, a selective serotonin reuptake inhibitor, is widely used in the clinical treatment of depression. While several antidepressants show promise as geroprotectors, the role of paroxetine in aging remains unclear. In this study, we evaluated the lifespan extension effect of paroxetine in Caenorhabditis elegans ( C. elegans ) and elucidated the underlying mechanisms. The results showed that paroxetine can prolong lifespan concomitant extension of healthspan as indicated by increasing mobility and reducing lipofuscin accumulation, as well as confer protection to nematodes against different abiotic stresses. Paroxetine upregulated ser-7 expression and downregulated dop-4 expression. dop-4 RNA interference (RNAi) mimicked the beneficial effect of paroxetine on lifespan. Conversely, ser-7 RNAi abolished paroxetine-induced lifespan extension and the expression changes of dop-4 and genes related to insulin/insulin-like growth factor 1 signaling (IIS). Moreover, paroxetine exhibited a comparable lifespan extension effect to that observed in daf-2 or age-1 mutants; however, this effect was abolished in daf-16 mutant. Taken together, these results suggest that paroxetine promotes health and longevity in C. elegans through the ser-7 - dop-4 -IIS pathway, underscoring its potential as a geroprotector.
Ganoderma atrum is an edible and medicinal fungi in oriental countries with various bioactivities, such as antioxidant, anti-inflammatory and anti-aging properties. The study was to evaluate the effects of polysaccharide from Ganoderma atrum (PSG) on lifespan, healthspan (locomotion, pumping, lipofuscin, ROS, chemotaxis and intestinal permeability) and defense system (stress resistance, antioxidant enzymes activities), as well as to investigate its anti-aging mechanism in Caenorhabditis elegans . The findings indicated that PSG prolonged the lifespan (optimal concentration at 400 μg/mL, with an increased average lifespan by 23.10 %) and improved senescence-related physiological indicators of worms. Furthermore, the lipid accumulation was reduced, while stress resistance and antioxidant enzymes activities were enhanced after PSG intervention. Meanwhile, studies with mutants demonstrated that DAF-16/FOXO and SKN-1/Nrf-2 were required for lifespan-extension, which might be attributed to the IIS and MAPK pathways. Overall, these demonstrated that PSG was a potential dietary supplement to promote health and ameliorate aging-associated pathologies.
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