Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in the treatment of aging-related diseases. Sirtuin 1 (SIRT1), a member of NAD+-dependent deacetylase enzyme family, is extensively explored as a potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against aging-related diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) and reperfusion (MI/R), Atherosclerosis (AS), and Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, SIRT1 regulates cellular senescence and multiple aging-related cellular processes, including SIRT1/Keap1/Nrf2/HO-1 and SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB and SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP and SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mediated mitochondrial damage, SIRT1/FoxO mediated autophagy, and SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin mediated neuroprotective effects. In this review, we summarized the role of SIRT1 in the improvement of the attenuation effect of quercetin on aging-related diseases and the relationship between relevant signaling pathways regulated by SIRT1. Moreover, the functional regulation of quercetin in aging-related markers such as oxidative stress, inflammatory response, mitochondrial function, autophagy and apoptosis through SIRT1 was discussed. Finally, the prospects of an extracellular vesicles (EVs) as quercetin loading and delivery, and SIRT1-mediated EVs as signal carriers for treating aging-related diseases, as well as discussed the ferroptosis alleviation effects of quercetin to protect against aging-related disease via activating SIRT1. Generally, SIRT1 may serve as a promising therapeutic target in the treatment of aging-related diseases via inhibiting oxidative stress, reducing inflammatory responses, and restoring mitochondrial dysfunction.

The fertility of female animals is negatively correlated with increasing chronological age. In aging broiler breeder hens, there is a decline in the functionality of the ovary and liver accompanied by hormonal or endocrine changes, a reduction in antioxidant capacity, and a decrease in folliculogenesis. Therefore, improving the reproductive function in aging breeder hens using dietary strategies is of great concern to the poultry breeder. This study evaluated the capacity of dietary quercetin (Q), vitamin E (VE), and their combination (Q + VE) to promote follicle development and attenuate organ inflammation by improving the antioxidant capacity of aging breeder hens. In this study, 400 broiler breeder hens (Tianfu broilers breeder hens, 435 days old) were allotted into four groups (100 birds each) with four replicates each (25 birds each). They were fed diets containing Q (0.4 g/kg), VE (0.2 g/kg), Q + VE (0.4 g/kg + 0.2 g/kg), and a basal diet for 10 weeks. The results showed that Q + VE improved the organ characteristics (p < 0.05), and also that Q + VE showed protective effects on the liver against injury, as well as increasing the antioxidant capacity of the liver, serum, and ovary (p < 0.05). Furthermore, liver lipid synthesis was increased remarkably, as indicated by the changes in triglyceride levels in hens fed Q + VE (p < 0.05). Levels of E2, FSH, and LH, their receptors, and mRNAs related to yolk precursor synthesis were increased by the Q + VE (p < 0.05). Therefore, the combination of quercetin and vitamin E synergistically promotes and regulates the transportation and exchange of synthetic substances among the liver–blood–ovary alliances to ensure the synchronous development and functional coordination between the liver and ovary in aging breeder hens.

Laying hens experience a rapid decline in egg production, egg quality, and immunity, usually at the end of the peak laying period. Quercetin, a known flavonoid, exerts biological activities, including phytoestrogenic, immunity, antibiotic, antioxidant, and anti-inflammatory properties. Vitamin E also shows egg production and immunoregulatory potential in animals. This study evaluated the capacity of dietary quercetin, vitamin E, and the combination of both, to promote egg production and egg quality, and to improve the immunity of aging breeder hens. We also elucidated how quercetin and vitamin E combination could synergistically affect egg production, egg quality, and immunity in aging breeder hens. A total of 400 Tianfu broiler breeders at the age of 52 wk were randomly allotted to 4 treatments with 4 replicates, 100 hens per treatment and 25 hens per replicate. They were fed diets containing quercetin at 0.4 g/kg, Vitamin E (200 mg/kg), quercetin and vitamin E (0.4 g/kg and 200 mg/kg), and a basal diet (control) for a period 10 wk. Daily feed intake and egg production rate were recorded, and weekly records were recorded on egg quality tests. At the end of the 10-wk experimental period, blood samples and immune organ (spleen) were collected from 2 birds per replicate, totaling 32 birds. Feed intake, immune organ index, serum cytokines, and immunoglobulins were evaluated, and the mRNA expression of genes related to immunity was determined from the spleen tissue. Generally, the results showed that separately or as a combination, supplemental quercetin and vitamin E significantly improved performance and egg quality ( P < 0.05), and significantly increased serum immunoglobulins (IgA, IgM, and IgG) and cytokines (IFN-γ and IL-2) concentrations, as well as promoted immune organ development and index, and promoted the expression of splenic immune-related genes (IL-2 and INF-γ) ( P < 0.05), compared with the control. It was confirmed in this study that the combination of quercetin and vitamin E exert synergistic effects on egg production, egg quality, and immune function in aging hens.

Several reproductive hormones were reported to be involved in regulating egg yolk precursor synthesis in chickens; however, the mechanism that shows how the liver-blood-ovary signal axis works in relation to age changes has not been reported yet. Therefore, in this study, we observe the morphology and histology of the liver and ovary and determine the serum biochemical parameters and the expression abundance of the critical genes from d90 to 153. Results show that the body weight and liver weight were significantly increased from d132, while the ovary weight increased from d139. Aside from the increase in weight, other distinct changes such as the liver color and an increased deposition of large amounts of yolk precursors into the ovarian follicles were observed. On d139, we observed small fatty vacuoles in the hepatocytes. The results of serum biochemical parameters showed a significant increase in the estradiol (E2) level, first on d125, and then it reached its peak on d132. Meanwhile, the levels of follicle-stimulating hormone (FSH) increased initially and then remained at a high level from d146 to d153, while the levels of luteinizing hormone (LH) increased significantly on d132 and reached the top level on d153. Moreover, the levels of lecithin (LEC), vitellogenin (VTG), very low density lipoprotein y (VLDLy), triglyceride (TG), and total cholesterol (TC) were significantly increased at d125 and were close from d146 to d153. The mRNA and protein expression of estrogen receptor-alpha (ER-α) and E2 levels in the liver and serum, respectively, showed similar changes. Moreover, with reference to an increase in serum E2 level, the mRNA expression of genes related to yolk precursor synthesis (very low density apolipoprotein-II, ApoVLDL-II) and vitellogenin-II (VTG-II), lipogenesis (fatty acid synthase, FAS), and lipid transport (microsomal triglyceride transport protein, MTTP) in the liver showed up-regulation. These results suggest that the correlation between liver-blood-ovary alliances regulate the transport and exchange of synthetic substances to ensure synchronous development and functional coordination between the liver and ovary. We also found that E2 is an activator that is regulated by FSH, which induces histological and functional changes in the hepatocytes through the ER-α pathway.

The importance of gut health in animal welfare and wellbeing is undisputable. The intestinal microbiota plays an essential role in the metabolic, nutritional, physiological, and immunological processes of animals. Therefore, the rapid development of dietary supplements to improve gut functions and homeostasis is imminent. Recent studies have uncovered the beneficial effects of dietary supplements on the immune response, microbiota, gut homeostasis, and intestinal health. The application of citrulline (a functional gut biomarker) and quercetin (a known potent flavonoid) to promote gut functions has gained considerable interest as both bioactive substances possess anti-inflammatory, anti-oxidative, and immunomodulatory properties. Research has demonstrated that both citrulline and quercetin can mediate gut activities by combating disruptions to the intestinal integrity and alterations to the gut microbiota. In addition, citrulline and quercetin play crucial roles in maintaining intestinal immune tolerance and gut health. However, the synergistic benefits which these dietary supplements (citrulline and quercetin) may afford to simultaneously promote gut functions remain to be explored. Therefore, this review summarizes the modulatory effects of citrulline and quercetin on the intestinal integrity and gut microbiota, and further expounds on their potential synergistic roles to attenuate intestinal inflammation and promote gut health.