2,5-Dimethyl-Celecoxib ExtendsDrosophilaLife Span via a Mechanism That Requires Insulin and Target of Rapamycin Signaling

Abstract

The search for antiaging drugs is a key component of gerontology research. A few drugs with positive effects on life span in model organisms have been found. Here, we report that 2,5-dimethyl-celecoxib, a derivative of the anti-inflammatory drug celecoxib, can extend Drosophila life span and delay aging by a mechanism involving insulin signaling and target of rapamycin signaling. Importantly, its positive effects were apparent when the treatment window was restricted to the beginning of life or the later half. 2,5-Dimethyl-celecoxib-induced longevity was also associated with improvements in physical activity, intestinal integrity, and increased autophagy. In addition, 2,5-dimethyl-celecoxib exhibited protective effects against several kinds of stress such as starvation and heat. The generally positive effects of 2,5-dimethyl-celecoxib on both health and life span, combined with its mode of action via evolutionarily conserved signaling pathways, indicate that it has the potential to become an effective antiaging drug.

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians

“…Transgenic flies obtained were named UAS-atg18a. These transgenic flies were first made isogenic and then crossed to GeneSwitch-gal4 flies (gift of Sichuan Agricultural University) to induce the expression of the transgene under RU486 (w/v, 200 µM; Sigma-Aldrich, CAS 84371-65-3) control (Wu et al 2016). The mating of UAS-atg18a with GeneSwitch-gal4 produced F1 flies with genome type of GS-gal4/+; UAS-atg18a/+.…”

CO2 anesthesia on Drosophila survival in aging research

“…The starvation test was performed on medium containing 5 g agar, 9 g ethyl p‐hydroxybenzoate, 30 ml 95% ethanol, 6 ml propionic acid, 0.73 g anhydrous calcium chloride per liter (Wu et al, ). Ten‐day‐old flies were put on the starvation culture medium, with 20 flies per vial and four replicates in each group.…”

Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

“…AKT plays important roles in neuronal survival, growth, polarity, synaptic plasticity and circuitry. Dysregulation of the AKT is the basis of many neurodevelopmental, neurocognitive, neuropsychiatric and neurodegenerative diseases [56]. Many studies have already proved that pharmacological inhibition of AKT activity can increase lifespan and healthspan in Drosophila [57].…”