撰文丨王聪 编辑丨王多鱼 排版丨水成文 临床研究发现， 自闭症 患者的外周组织存在多种 线粒体紊乱 。然而，神经元代谢如何导致自闭症相关表型，目前仍不清楚。 2025 年 9 月 3 日，空军军医大学 （ 第四军医大学） 武胜昔 教授、 王亚周 教授团队在 Cell 子刊 Cell Metabolism 上发表了题为： Mitochondrial dysfunction reveals H 2 S-mediated synaptic sulfhydration as a potential mechanism for autism-associated social defects 的研究论文。 该研究表明， 线粒体功能障碍 导致 H₂S 水平升高， 介导了 突触蛋白 mGluR5 的 硫巯基化修饰 （ Sulfhydration ） ，这可能是自闭症相关社交缺陷的一种潜 在机制。 在这项最新研究中，研究团队重点关注了 前扣带回皮层 （ACC） ，并报告了在 Shank3b −/− 和 Fmr1 −/y 神经元中线粒体功能障碍的共同结果是 硫化氢 （ H₂S ） 水平升高。在野生型小鼠中，ACC 中 胱硫醚 ...

Core Viewpoint - CAR-T cell therapy is one of the most promising cancer treatment methods, but its efficacy is significantly limited by aging-related factors, particularly the decline in nicotinamide adenine dinucleotide (NAD) levels, which drives CAR-T cell failure [2][8]. Group 1: Research Findings - A study published by researchers from the University of Lausanne and Geneva University Hospitals indicates that restoring NAD levels can enhance the therapeutic effects of aging CAR-T cells, providing a promising approach to improve CAR-T therapy [2][8]. - The study demonstrates that aging is a limiting factor for effective CAR-T cell responses, with evidence showing that CAR-T cells derived from aged female mice exhibit mitochondrial dysfunction due to NAD depletion, leading to poor stem-like characteristics and impaired anti-tumor function [7][8]. - Human data analysis further supports that both age and NAD metabolism influence the response to CAR-T cell therapy, highlighting the potential of targeting NAD pathways to restore mitochondrial health and function in CAR-T cells from older patients [7][8]. Group 2: Importance of NAD in T Cell Function - NAD metabolism plays a critical regulatory role in T cell fate and function, with alterations in NAD homeostasis linked to impaired T cell responses [5][6]. - Aging is a primary risk factor associated with cancer, with approximately 75% of cancer patients eligible for immunotherapy being over 65 years old, indicating the need for strategies that address age-related declines in treatment efficacy [5][6]. - The maintenance of stem cell-like T cell populations is crucial for the success of CAR-T cell therapy, and recent studies suggest that enhancing mitochondrial metabolism through metabolic interventions can improve CAR-T cell efficacy [4][8].