Serine Deficiency Exacerbates Inflammation and Oxidative Stress via Microbiota-Gut-Brain Axis in D-Galactose-Induced Aging Mice

Abstract

Inflammation and oxidative stress play key roles in the process of aging and age-related diseases. Since serine availability plays important roles in the support of antioxidant and anti-inflammatory defense system, we explored whether serine deficiency affects inflammatory and oxidative status in D-galactose-induced aging mice. Male mice were randomly assigned into four groups: mice fed a basal diet, mice fed a serine-and glycine-deficient (SGD) diet, mice injected with D-galactose and fed a basal diet, and mice injected with D-galactose and fed an SGD diet. The results showed that D-galactose resulted in oxidative and inflammatory responses, while serine deficiency alone showed no such effects. However, serine deficiency significantly exacerbated oxidative stress and inflammation in D-galactose-treated mice. The composition of fecal microbiota was affected by Dgalactose injection, which was characterized by decreased microbiota diversity and downregulated ratio of Firmicutes/Bacteroidetes, as well as decreased proportion of Clostridium XIVa. Furthermore, serine deficiency exacerbated these changes. Additionally, serine deficiency in combination with D-galactose injection significantly decreased fecal butyric acid content and gene expression of short-chain fatty acid transporters (Slc16a3 and Slc16a7) and receptor (Gpr109a) in the brain. Finally, serine deficiency exacerbated the decrease of expression of phosphorylated AMPK and the increase of expression of phosphorylated NFκB p65, which were caused by D-galactose injection. In conclusion, our results suggested that serine deficiency exacerbated inflammation and oxidative stress in D-galactose-induced aging mice. The involved mechanisms might be partially attributed to the changes in the microbiotagut-brain axis affected by serine deficiency.

Serum Metabolomic Profiling Reveals the Amelioration Effect of Methotrexate on Imiquimod-Induced Psoriasis in Mouse

“…As the result of d-galactose treatment, the AGE content in the circulation of mice increased, and this further caused oxidative stress and increased inflammation. In addition, excessive d-galactose caused the overproduction of reactive oxygen species (ROS), which causes increased malondialdehyde (MDA) content and inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and IL-6), as well as activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione content in circulation ( Wang et al, 2020 ). These accompanying results of abnormal d-galacotose metabolism are in accordance with the pathogenesis of psoriasis ( Kopeć-Pyciarz et al, 2018 ).…”

Monotropein alleviates H2O2‑induced inflammation, oxidative stress and apoptosis via NF‑κB/AP‑1 signaling

“…Mtp anti-inflammatory effects are reversed by PMA. nF-κB is a key transcription factor associated with oxidative stress and the inflammatory response (13,14). AP-1 has been demonstrated to interact with nF-κB, and nF-κB/aP-1 signaling cascades serve an important role in inflammation (22,23).…”

“…Mtp induced the differentiation of bone marrow-derived endothelial progenitor cells and prevented cell apoptosis by decreasing the release of reactive oxygen species (roS) (12). nF-κB is a classical transcription factor that is activated in response to extracellular stimulus, and serves a crucial role in oxidative stress and inflammatory responses (13,14). He et al (15) demonstrated that Mtp significantly inhibited lipopolysaccharide (LPS)-induced secretion of inflammatory cytokines by suppressing activation of the nF-κB signaling pathway.…”

Verification of Resveratrol Inhibits Intestinal Aging by Downregulating ATF4/Chop/Bcl-2/Bax Signaling Pathway: Based on Network Pharmacology and Animal Experiment

“…Intestinal aging, often causes a series of chain reactions, such as intestinal inflammation, bacterial imbalance, immune deficiency, etc., which accelerate the intestinal aging (Kühn et al, 2020;Rampelli et al, 2020). Recent studies suggested that aging is mainly related to oxidative stress, cell apoptosis, autophagy and intestinal flora (Chen Y. et al, 2020;Wang F. et al, 2020;Xu et al, 2020). Resveratrol is one of compounds to slow aging.…”