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.

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.

In utero and lactational ß-carotene supplementation attenuates D-galactose-induced hearing loss in newborn rats.

D-Galactose could give rise to free radical damage by disturbing the some maternal antioxidants. The oxidative stress induced by D-galactose is a potent inducer of apoptosis, which is accompanied by the activation of protein-splitting enzymes called caspases. Apoptosis is a crucial physiological determinant of embryonic and neonatal development, and play an essential role in the development of the inner ear structures. Recently the increasing of D-galactose exposure is due to high consumption of dairy foods or reduced galactose metabolism. An overwhelming presence of D-galactose is known to become highly ototoxicity to humans. The purpose of this study was to investigate whether supplementation of pregnant and lactational mothers with ß-carotene could attenuate cochlear function damage and hair cells apoptosis induced by d-galactose in newborn rats. Pregnant rats were supplemented with D-galactose, or D-galactose and ß-carotene from gestational day (GD) 7 until postnatal day (PND) 21. On PND 22, offspring were examined in the distortion product otoacoustic emission (DPOAE) task, cochleae were then harvested for assessment of apoptosis by immunohistochemical stain for cysteine-aspartic acid proteases 3 (caspase-3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Maternal and offspring blood samples were then collected by direct cardiac puncture in heparin tubes, blood levels of D-galactose and ß-carotene were measured, plasma was separated for malondialdehyde (MDA) analysis, erythrocytes were left for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH). D-Galactose could significantly disturb the balance between maternal antioxidants and free radicals, and induce hearing loss in the offspring and cochlear hair cell apoptosis. In contrast, ß-carotene supplementation, coincidentally with D-galactose exposure, ameliorated these changes. Our data offer a conceptual framework for designing clinical trials using a safe micronutrient, ß-carotene, as a simple preventive strategy for D-galactose-induced ototoxicity.