Transcriptomic and metabolomic analyses reveal that lemon extract prolongs Drosophila lifespan by affecting metabolism.

Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.

Effect of Ejiao (Asini Corii Colla) and Turtle Carapace Glue on Gut Microbiota in Nude Mice with Uterine Fibroids Based on High-Throughput Sequencing of 16SrRNA Gene.

Objective: To observe the effects of Asini Corii Colla, turtle carapace glue, and other drugs on the intestinal flora of nude mice with uterine fibroids model, so as to provide evidence for the clinical application of drugs. Methods: Set up five groups: blank control group, turtle carapace glue group, turtle carapace glue and ejiao 4 : 1 mixed group, turtle carapace glue and ejiao 1 : 1 mixed group, and turtle shell glue and Salvia miltiorrhiza (danshen) 1 : 1 mixed group. Then, the model nude mice were fed ejiao, turtle carapace glue, and other corresponding drugs. Before administration, 2 weeks after administration, and 4 weeks after administration, the feces of the model nude mice were taken respectively, subpacked into labeled cryotubes, and stored at -80°C. All samples were sent for gene sequencing after completion. The differences in gut microbiota and abundance in different groups were compared by 16SrRNA segment sequencing. Results: ① There were differences in flora composition and a relative abundance among the groups, but the strains with a high relative abundance were Bacteroides, Firmicutes, and Proteobacteria; ② there were significant differences in the community structure and composition of intestinal flora between nude mice treated for 4 weeks and those not treated (p < 0.05); ③ after 4 weeks of administration, the relative abundance of Bacteroidetes in each group was higher than that before administration, and the relative abundance of Firmicutes decreased. Conclusion: Asini Corii Colla, turtle carapace glue, and other drugs with different compatibility ratios can change the composition of intestinal flora in nude mice with uterine fibroids to a certain extent; the decrease in the relative abundance of Firmicutes and the increase in the relative abundance of Bacteroidetes were important structural changes of intestinal flora in nude mice at 4 weeks after administration.

Glutamine Availability Regulates the Development of Aging Mediated by mTOR Signaling and Autophagy.

Glutamine is a conditionally essential amino acid involved in energy production and redox homeostasis. Aging is commonly characterized by energy generation reduction and redox homeostasis dysfunction. Various aging-related diseases have been reported to be accompanied by glutamine exhaustion. Glutamine supplementation has been used as a nutritional therapy for patients and the elderly, although the mechanism by which glutamine availability affects aging remains elusive. Here, we show that chronic glutamine deprivation induces senescence in fibroblasts and aging in Drosophila melanogaster, while glutamine supplementation protects against oxidative stress-induced cellular senescence and rescues the D-galactose-prompted progeria phenotype in mice. Intriguingly, we found that long-term glutamine deprivation activates the Akt-mTOR pathway, together with the suppression of autolysosome function. However, the inhibition of the Akt-mTOR pathway effectively rescued the autophagy impairment and cellular senescence caused by glutamine deprivation. Collectively, our study demonstrates a novel interplay between glutamine availability and the aging process. Mechanistically, long-term glutamine deprivation could evoke mammalian target of rapamycin (mTOR) pathway activation and autophagy impairment. These findings provide new insights into the connection between glutamine availability and the aging process.

Transcriptome analysis reveals differentially expressed genes associated with high rates of egg production in chicken hypothalamic-pituitary-ovarian axis.

The hypothalamic-pituitary-ovarian (HPO) axis regulates the breeding process cycle of laying hens. However, the key regulatory genes of the HPO axis and pathways that drive chicken egg laying performance remain elusive. A total of 856 Chinese Luhua chicken was raised and the highest two hundred and the lowest two hundred chicken egg production were considered as high egg production (HEP) and low egg production (LEP) according to the total egg number at 300 days of age, respectively. RNA-seq sequencing (RNA-Seq) was conducted to explore the chicken transcriptome from the hypothalamus, pituitary gland and ovary tissue of 6 Chinese Luhua chicken with 3 high and low-rate egg production. In total, 76.09 Gb RNA-seq sequences were generated from 15 libraries with an average of 5.07 Gb for each library. Further analysis showed that 414, 356 and 10 differentially expressed genes (DEGs) were identified in pituitary gland, ovary and hypothalamus between HEP and LEP chickens, respectively. In pituitary gland, DEGs were involve in regulation of cellular glucose homeostasis, Ras protein signal transduction, negative regulation of hormone secretion. In Ovary DEGs were mainly involved in embryonic organ development, regulation of canonical Wnt signaling, response to peptide hormone. Our study identified DEGs that regulate mTOR signaling pathway, Jak-STAT signaling pathway, Tryptophan metabolism and PI3K-Akt signaling pathways at HPO-axis in laying hens. These important data contribute to improve our understanding of reproductive biology of chicken and isolating effective molecular markers that can be used for genetic selection in Chinese domestic Luhua chicken.

Alpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPK.

Alpha-ketoglutarate (AKG) is a key metabolite of the tricarboxylic acid (TCA) cycle, an essential process influencing the mitochondrial oxidative respiration rate. Recent studies have shown that dietary AKG reduces mTOR pathway activation by inhibiting ATP synthase, thereby extending the lifespan of nematodes. Although AKG also extends lifespan in fruit flies, the antiaging mechanisms of AKG in these organisms remain unclear. In the present study, we explored changes in gene expression associated with the extension of Drosophila lifespan mediated by dietary AKG. Supplementation of the flies' diets with 5 µM AKG extended their lifespan but reduced their reproductive performance. Dietary AKG also enhanced vertical climbing ability, but did not protect against oxidative stress or increase tolerance to starvation. AKG-reared flies were resistant to heat stress and demonstrated higher expression of heat shock protein genes (Hsp22 and Hsp70) than control flies. In addition, AKG significantly upregulated mRNA expression of cry, FoxO, HNF4, p300, Sirt1 and AMPKα, and downregulated expression of HDAC4, PI3K, TORC, PGC, and SREBP. The metabolic effects of AKG supplementation included a reduction in the ATP/ADP ratio and increased autophagy. Collectively, these observations indicate that AKG extends Drosophila lifespan by activating AMPK signaling and inhibiting the mTOR pathway.