Diosgenin intervention: targeting lipophagy to counter high glucose diet-induced lipid accumulation and lifespan reduction.

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04017-3.

Fermented cereal-origin gerobiotic cocktails promote healthy longevity in Caenorhabditis elegans.

There is growing interest in dietary interventions, particularly gerobiotics, that directly target aging. Several single-strain gerobiotics have proven to be beneficial in alleviating aging and age-related functional declines across species, but multistrain/multispecies gerobiotics have been proven even more advantageous due to the potential synergy and additive effects among individual isolates. However, there is very limited research on how multistrain/multispecies gerobiotic combinations or cocktails extend healthy longevity. This study comprehensively analyzed probiotic bacteria from traditionally fermented Barnyard millet and compared their efficacy in promoting healthy longevity under various combinations using Caenorhabditis elegans. We have shown that dramatic lifespan extension can be achieved by combining gerobiotics, and the effect was found to be strictly strain-specific. Among the 120 combinations tested, we identified two synergistic gerobiotic combinations, cocktail 55 (combination of B. licheniformis PS70, L. delbrueckii subsp. bulgaricus PS77, and L. amylovorus PS60) and cocktail 112 (combination of L. delbrueckii subsp. bulgaricus PS77, L. lactis PS10, and P. pentosaceus PS91), extending the mean lifespan of C. elegans by up to 46.2% and 53.1%, respectively. Our mechanistic study showed that the life-promoting effect of cocktail 55 relied on the p38 MAPK-SKN-1 pathway, while cocktail 112 acted on multiple signaling pathways, including IIS, ß-catenin, and TGF-ß pathways, to achieve its impact on the host. Moreover, feeding gerobiotic cocktails improved several healthspan markers reported to decline with age. These observations showed that the gerobiotic cocktails target different subsets of the gene regulatory network controlling the aging process in C. elegans, thereby extending healthy longevity.

Multifaceted Chiral Probe 2,3-Dihydro-4-hydroxy-chromene Schiff Base in Detecting Cu2+ Ions, l-Histidine, and Indazole: Spectroscopic Investigation and Confocal and Live Cell Imaging.

2,3-Dihydro-4-hydroxy-chromene-4(N)-ethyl thiosemicarbazone (probe F4) is used as a chemosensor, and it selectively detected Cu2+ ions among the metal ions by showing fluorescence "TURN ON" behavior. The stoichiometric binding of the probe with Cu2+ (CF4) was confirmed by Job's plot and mass spectroscopy. Further, CF4 was used as a sensor for the detection of l-amino acids and N-heterocyclic compounds. Among them, CF4 selectively detected l-histidine by showing fluorescence "TURN-OFF" behavior and selectively detected indazole by showing fluorescence "TURN-ON" behavior. These behaviors were further confirmed by in vivo live cell imaging studies by using Caenorhabditis elegans as a model. In vitro cytotoxicity was assayed for probe F4, complex CF4, and CF4 with l-histidine and indazole. The IC50 concentration was used for confocal imaging studies by using the MDA-MB-231 cell line (breast cancer cell line).

p21-Activated kinase 1 (PAK1) in aging and longevity: An overview.

The p21-activated kinases (PAKs) belong to serine/threonine kinases family, regulated by ∼21 kDa small signaling G proteins RAC1 and CDC42. The mammalian PAK family comprises six members (PAK1-6) that are classified into two groups (I and II) based on their domain architecture and regulatory mechanisms. PAKs are implicated in a wide range of cellular functions. PAK1 has recently attracted increasing attention owing to its involvement in oncogenesis, tumor progression, and metastasis as well as several life-limiting diseases and pathological conditions. In Caenorhabditis elegans, PAK1 functions limit the lifespan under basal conditions by inhibiting forkhead transcription factor DAF-16. Interestingly, PAK depletion extended longevity and attenuated the onset of age-related phenotypes in a premature-aging mouse model and delayed senescence in mammalian fibroblasts. These observations implicate PAKs as not only oncogenic but also aging kinases. Therefore, PAK-targeting genetic and/or pharmacological interventions, particularly PAK1-targeting, could be a viable strategy for developing cancer therapies with relatively no side effects and promoting healthy longevity. This review describes PAK family proteins, their biological functions, and their role in regulating aging and longevity using C. elegans. Moreover, we discuss the effect of small-molecule PAK1 inhibitors on the lifespan and healthspan of C. elegans.

Absolute removal of ciprofloxacin and its degraded byproducts in aqueous solution using an efficient electrochemical oxidation process coupled with adsorption treatment technique.

Pharmaceutical-based contaminants are the major reasons for morbidity and mortality in aquatic animals and lead to several side effects and diseases in human community. Availability of proper, efficient, and cost-effective treatment technologies is still scarce. In this study, an efficient combined treatment technique (electrochemical oxidation and adsorption processes) was developed for the complete detoxification of most commonly used antibiotic, ciprofloxacin in aqueous solution. Electrochemical degradation of ciprofloxacin was performed using titanium-based tri-metal oxide mesh type anode, and the effective oxidative potential, electrolysis time, and pH for the degradation of ciprofloxacin were thoroughly evaluated. Sulfate, fluoride ions and toxic byproducts generated during electrochemical oxidation of ciprofloxacin were subsequently removed through a simple adsorption treatment using activated charcoal for 90 min. Further, the toxicity of the treated water was assessed with the nematode Caenorhabditis elegans species at different time intervals by observing the expressions of important stress-responsive genes viz., sod-3, hsp-16.2, ctl-1,2,3 and gst-4. The results exhibited that the combined process of electrochemical oxidation and adsorption treatment is simple, low-cost as well as effective to eliminate ciprofloxacin and its toxic byproducts in aqueous solution.

Anthelmintic efficacy of glycolipid biosurfactant produced by Pseudomonas plecoglossicida: an insight from mutant and transgenic forms of Caenorhabditis elegans.

The current research focuses on the production and characterization of glycolipid biosurfactant (GB) from Pseudomonas plecoglossicida and its anthelmintic activity against Caenorhabditis elegans. The GB was purified and characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography and Mass Spectrometry (GC-MS) analysis. Anthelmintic activity of GB was studied at six different pharmacological doses from 10 to 320 µg/mL on C. elegans. Exposure of different developmental stages (L1, L2, L3, L4 and adult) of C. elegans to the GB reduced the survivability of worms in a dose and time-dependent manner. Adult and L4 worms were least susceptible, while L1, L2 and L3 were more susceptible to GB when compared to the untreated control. An increased exposure period drastically reduced the survival rate of worms and reduction in LC50 value. The GB significantly inhibited the development of C. elegans with an IC50 value of 53.14 µg/mL and even reduced the adult body length and egg hatching. Fecundity rate of the worms treated with GB at 20, 40 and 80 µg/mL decreased from 261.90 ± 3.21 to 239.70 ± 5.58, 164.20 ± 5.94 and 44.80 ± 6.22 eggs per worm, respectively. Besides the toxicological effects, prolonged exposure to GB significantly decreased (p ≤ 0.0001) the lifespan of wild type worms under standard laboratory conditions. Additionally, GB was found to be lethal towards ivermectin and albendazole resistant C. elegans strains. Overall, the data indicated that the GB extracted from P. plecoglossicida could be utilized for the control of non-susceptible and resistant gastrointestinal nematodes towards broad spectrum anthelmintic drugs, ivermectin and albendazole.

Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways.

Mild stress activates the adaptive cellular response for the subsequent severe stress called hormesis. Hormetic stress plays a vital role to activate multiple stress-responsive genes for the benefit of an organism. In tropical regions of world, tubers of Dioscorea spp. has been extensively used in folk medicine and also consumed as food. In this study, we report that the phytochemicals of Dioscorea alata L., tubers extends the lifespan of nematode model Caenorhabditis elegans by hormetic mechanism. We showed that the low dose of tubers extract at 200 and 300 µg/mL extends the mean lifespan of wild-type worms, whereas higher doses are found to be toxic. Supplementation of tubers extract slightly increased the intracellular ROS in second-day adult worms and it might activate the adaptive stress response, which protects the worms from oxidative and thermal stress. Transgenic reporter gene expression assay showed that extract treatment enhanced the expression of stress protective genes such as hsp-16.2, hsp-6, hsp-60 and gst-4. Further studies proved that the transcription factors HSF-1 and SKN-1/Nrf2 were implicated in hormetic stress response of the worms. Moreover, pretreatment of extract reduced the high glucose-mediated lipid accumulation by enhancing the expression of glyoxalase-1. It was also found that the aggregation of Parkinson's related protein α-synuclein reduced in the transgenic strain NL5901 and extended its lifespan. Finally, our results concluded that the presences of hormetic dietary phytochemicals in tubers might drive the stress response in C. elegans via HSF-1 and SKN-1/Nrf2 signaling pathways.