Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largelyunknown. This work highlights the importance of metabolic homeostasis in protecting again...Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largelyunknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine.By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, includingfree SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cysredox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteinsmodified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved inimmunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasingwith age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cysmodifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signalingpathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidativestress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. Thiswork decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulatorsof oxidative stress and redox signaling.展开更多
基金supported by the National Key R&D Program of China(no.2022YFA1303200)the National Natural Science Foundation of China(nos.82073221,32201216,and 31870826)+2 种基金the Science and Technology Project of Sichuan Province(nos.2024YFFK0099,2023NSFSC1525,and 2021YFS0134)the National Clinical Research Center for Geriatrics at West China Hospital(no.Z2024JC002)the West China Hospital 135 project(nos.ZYYC23013 and ZYYC23025).
文摘Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largelyunknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine.By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, includingfree SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cysredox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteinsmodified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved inimmunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasingwith age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cysmodifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signalingpathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidativestress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. Thiswork decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulatorsof oxidative stress and redox signaling.
