Masoprocol

Aging is associated with increased severity of inflammatory bowel disease (IBD). Gut senescence and altered environmental factors contribute to changes in the intestinal metabolome, particularly in frail older individuals. However, the role of age-associated dysbiosis, characterized by a decline in beneficial gut microbiota and their metabolites, in exacerbating IBD remains unclear.

To investigate the impact of aging-associated dysbiosis on colitis development, we employed fecal microbiota transplantation (FMT) in wild-type and IL-10-deficient mice. Aged mice were treated with gut microbiota from either young or aged mice and then subjected to dextran sulfate sodium (DSS) to induce experimental colitis. 16S rDNA sequencing and metabolomics were used to analyze microbial and metabolite profiles. Single-cell RNA sequencing (scRNA-seq) was performed to characterize lamina propria CD45⁺ immune cell composition.

Aged mice receiving microbiota from young mice exhibited less severe colitis than those receiving microbiota from aged mice, as evidenced by reduced disease activity, weight loss, and colonic shortening. Besides, aged mice displayed a significant decrease in the Lactobacillus population, accompanied by a reduction in Nordihydroguaiaretic acid (NDGA) levels. Decreased fecal NDGA levels were also observed in both IBD patients and elderly individuals. Administration of NDGA alleviated experimental colitis by downregulating the GSDMD/NR4A1/NLRP3 axis-mediated macrophage pyroptosis. Deletion of GSDMD in macrophages significantly diminished the protective effect of NDGA on colitis.

Our findings demonstrate that aging is associated with dysbiosis and reduced NDGA production, which increases susceptibility to intestinal inflammation. Gut microbial NDGA exhibits potential anti-inflammatory activity in colitis, suggesting a promising therapeutic target for aged-related IBD.

Drought is the main environmental factor limiting global crop yield in various abiotic stresses. Improving drought resistence of sweetpotato is necessary to ensure food security in the future climate scenarios. In this study, for Yanshu25 (Yan25, drought-tolerant cultivar), the genes related to jasmonic acid (JA) biosynthesis were significantly up-regulated by drought with relative higer endogenous JA content, while for Xushu32 (Xu32, drought-sensitive cultivar), the genes related to abscisic acid (ABA) biosynthesis were up-regulated by drought with relative higer endogenous ABA content. The coordinated regulation between JA and ABA on drought tolerance of sweetpotato was further carried using JA and ABA biosynthesis inhibitors--nordihydroguaiaretic acid (NDGA) or fluridone (FLU). Application of FLU or NDGA to drought-treated sweetpotato plants led to lower photosynthetic parameters and the activities of superoxide dismutase and peroxidase, and higher cell membrane damage under drought stress (D). For Xu32, under drought stress, FLU induced endogenous JA accumulation with lower expression level of JA signal transduction gene IbJAZ7, while NDGA did not affect ABA accumulation. FLU + JA recovered drought tolerance, as indicated by a significant increase of ABA content from D-FLU treatment, speculating that exogenous JA could promote endogenous ABA production. NDGA + ABA restored drought tolerance, as indicated by a significant up-regulation of JA and ABA contend from D treatment, speculating that endogenous ABA could also promote JA production and weaken NDGA inhibition. These results were in accordance with the expression trends of genes related to biosynthesis and signal transduction of JA and ABA. For Yan25, NDGA treatment increased leaf endogenous ABA content, and FLU treatment did not affect leaf JA accumulation. However, FLU + JA restored drought tolerance with higer ABA content and expressions of ABA-related genes. These results suggested that drought-sensitive sweetpotato was more dependent on ABA regulation pathway, and drought-tolerant sweetpotato was more dependent on JA regulation pathway under drought stress. In addition, there were positive feedback mechanisms of JA and ABA in sweetpotato in response to drought stress. Moreover, the function of IbAOS in sweetpotato roots was investigated and the results showed that IbAOS might improve drought tolerance by regulating JA biosynthesis. These results provided key information for further study of its role in tuberous root differentiation.