生物黑客、AI医疗

免疫系统每天都在慢性自杀：NAD+是唯一能踩刹车的救命分子

#NAD＋ #免疫系统 #慢性炎症 #NAD前体
11K
你的免疫系统每天开火1000次保你小命，但同样这套系统正在把你往坟墓里推，服不服？

炎症是把双刃剑，急性炎症救你命，慢性炎症要你命。科学家2000年造了个词叫“炎性衰老”，专门描述这种年龄相关的低度炎症状态。NAD+是细胞里的关键辅酶，既能产能量又能踩刹车控制炎症，但40岁后NAD+水平掉了一半，等于把刹车片拆了。临床研究发现吃NR这类NAD+前体能把血液里的炎症指标往下压，但到底能不能让你多活几年，现在还没人敢打包票。

炎症系统本质上是身体自带的暴力安保团队

炎症这件事往根上说就是免疫系统在干活。你划了道口子，它派白细胞冲过去，血管扩张让血流加速，红肿热痛全来了。这套流程从你祖宗十八代之前就刻在基因里，没有这套系统你连个纸片划伤都可能败血症挂掉。所以别一听炎症就觉得是坏事，急性炎症是你身体最能打的兄弟，随叫随到干活利索。

问题是这套安保系统有个致命bug。它设计出来是为了应对突发威胁，不是让你长期开着。就像消防队天天出警救火没问题，但要是城市每时每刻都在冒烟，消防队累死不说，整个城市也得烧光。免疫系统长期处于激活状态，各种促炎因子在血液里飘着，这些信号分子时刻提醒免疫细胞准备干活，时间一长就把正常组织也误伤了。

炎症反应分两种完全不同的模式。急性炎症来势猛去得快，几天完事身体恢复如初。慢性炎症悄无声息持续数月甚至数年，你压根感觉不到它在干活，但它从内部一点一点啃食你的器官。最要命的是慢性炎症几乎没有症状，很多人直到查出心脏病糖尿病才知道自己体内一直在“发火”。

急性炎症是救火队而慢性炎症就是纵火犯

救火队的逻辑很简单。你受伤了，免疫细胞像打了鸡血一样往伤口冲，释放组胺让血管壁漏缝，好让更多白细胞和营养物质渗到组织里。红肿热痛就是这套流程的外在表现，看着吓人但实际上是身体在自救。病原体被干掉，死细胞被清理，新组织开始长，一切都在几天内收工。

纵火犯的逻辑就阴险多了。没有明显的伤口或感染源，但免疫系统就是关不掉开关。原因五花八门，吃太油腻睡太少压力大，或者干脆就是年纪大了细胞自己出了问题。那些老化的细胞不死亡也不干活，赖在组织里疯狂往外吐炎症信号，周围的好细胞被拖下水也跟着发炎。

这两种炎症的根本区别在于有没有“关闭按钮”。急性炎症的按钮好使，威胁没了就按下去。慢性炎症的按钮要么坏了要么卡住了，要么干脆就是按了也没反应。你的身体在持续的低度炎症状态里泡着，免疫细胞累得要死，正常组织被误伤，修复机制跟不上破坏速度。这就是为什么慢性炎症被科学家称为“万病之源”。

炎性衰老是免疫系统长期误伤自己的鬼打墙状态

2000年意大利免疫学家弗兰切斯基造了这个词，精准概括了年龄增长伴随的慢性低度炎症。这哥们把免疫衰老和炎症两个概念缝一块了，指出了个残酷事实——你变老的过程就是免疫系统越来越不靠谱的过程。

免疫系统不靠谱体现在两方面。一方面是识别能力下降，该打的打不过，不该打的往死里打。另一方面是调控能力变差，炎症信号发出去之后收不回来。年轻的时候免疫系统像一支训练有素的军队，打完仗就地休整。老了之后这军队就跟吃了兴奋剂一样，看谁都像敌人，打完一波还要再来一波。

炎性衰老最邪门的地方在于它自己给自己续命。炎症损伤细胞，受损细胞释放更多炎症信号，更多炎症信号招来更多免疫细胞，更多免疫细胞制造更多损伤。这个正反馈循环一旦启动，就像滚雪球一样根本停不下来。你体内的C反应蛋白、白介素6、肿瘤坏死因子这些炎症指标逐年爬升，它们就是那场看不见的火灾冒出来的烟。

NAD+是细胞燃烧引擎同时也是炎症系统的刹车片

NAD+这玩意儿你体内每个细胞都有，学名叫烟酰胺腺嘌呤二核苷酸。它最出名的活儿是帮线粒体把食物转化成能量，没它你连喘气都费劲。但它还有另一份兼职，当细胞内炎症信号的刹车片。

细胞里有一套叫sirtuins的蛋白，专门负责给各种炎症开关去活化，而sirtuins没NAD+就动不了。

问题出在NAD+水平会随年龄往下掉。三十岁之后每年掉一点，到四十岁可能只剩年轻时的一半。更坑的是发炎状态本身会加速NAD+的消耗。细胞里有个叫CD38的酶，发炎的时候特别活跃，它会把NAD+像吃零食一样拆掉。还有一个叫PARP的酶，DNA受损时大量消耗NAD+去修东西。你年纪越大DNA损伤越多，炎症越厉害CD38越活跃，NAD+被两头夹击。

这局面就像你开着一辆刹车片越来越薄的车，同时还老踩油门。NAD+少了，sirtuins干不了活，炎症刹不住。炎症越刹不住，CD38越活跃，NAD+掉得越快。一套标准的恶性循环，越老越炎，越炎越老。科学家把这种双向关系叫“炎性衰老循环”，你在里面转得越久身体垮得越快。

临床研究显示补NAD+确实能把炎症指标摁下去

过去几年有好几项人体试验在干同一件事——让不同的人吃NR这种NAD+前体，然后抽血看炎症指标变了没。结果总体上指向一个方向：炎症信号被压低了，而且压得还挺明显。

2019年那项研究让超重的老年男性每天吃1000毫克NR，21天后血液里的白介素6和肿瘤坏死因子明显下降。2020年心衰病人吃5到9天NR，NLRP3炎症小体的基因表达被摁住了，连带白介素1β和白介素18也跟着降。红斑狼疮病人吃一周NR，免疫细胞对Toll样受体4的过度反应被削了。银屑病患者吃四周NR，血液里的C反应蛋白和中性粒细胞数量都下来了。帕金森病人吃四周NR，脑脊液里的好几种炎症细胞因子都掉了。

这些研究覆盖了健康老人、胖人、心衰患者、自身免疫病患者、神经退行病患者，跨度够大。用的都是1000到2000毫克每天的剂量，时间最短一周最长十二周。虽然研究对象不一样测量方法也不完全统一，但出来的结果方向高度一致——NR能把炎症信号的音量调低。


References

  1. Karpuzoglu, E., Holladay, S. D., & Gogal, R. M. (2025). Inflammaging: triggers, molecular mechanisms, immunological consequences, sex differences, and cutaneous manifestations. Frontiers in Immunology, 16, 1704203. https://doi.org/10.3389/fimmu.2025.1704203
  2. Andonian, B. J., Hippensteel, J. A., Abuabara, K., Boyle, E. M., Colbert, J. F., Devinney, M. J., Faye, A. S., Kochar, B., Lee, J., Litke, R., Nair, D., Sattui, S. E., Sheshadri, A., Sherman, A. N., Singh, N., Zhang, Y., & LaHue, S. C. (2025). Inflammation and aging-related disease: A transdisciplinary inflammaging framework. GeroScience, 47(1), 515–542. https://doi.org/10.1007/s11357-024-01364-0
  3. Pugel, A. D., Schoenfeld, A. M., Alsaifi, S. Z., Holmes, J. R., & Morrison, B. E. (2024). The Role of NAD+ and NAD+-Boosting Therapies in Inflammatory Response by IL-13. Pharmaceuticals, 17(2), 226. https://doi.org/10.3390/ph17020226
  4. Elhassan, Y. S., Kluckova, K., Fletcher, R. S., Schmidt, M. S., Garten, A., Doig, C. L., Cartwright, D. M., Oakey, L., Burley, C. V., Jenkinson, N., Wilson, M., Lucas, S. J. E., Akerman, I., Seabright, A., Lai, Y.-C., Tennant, D. A., Nightingale, P., Wallis, G. A., Manolopoulos, K. N., … Lavery, G. G. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports, 28(7), 1717-1728.e6. https://doi.org/10.1016/j.celrep.2019.07.043
  5. Chavda, V. P., Feehan, J., & Apostolopoulos, V. (2024). Inflammation: The Cause of All Diseases. Cells, 13(22), 1906. https://doi.org/10.3390/cells13221906
  6. Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A. A., Hirokawa, K., Witkowski, J. M., & Franceschi, C. (2023). Immunology of Aging: the Birth of Inflammaging. Clinical Reviews in Allergy & Immunology, 64(2), 109–122. https://doi.org/10.1007/s12016-021-08899-6
  7. Margină, D., Ungurianu, A., Purdel, C., Tsoukalas, D., Sarandi, E., Thanasoula, M., Tekos, F., Mesnage, R., Kouretas, D., & Tsatsakis, A. (2020). Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors. International Journal of Environmental Research and Public Health, 17(11), 4135. https://doi.org/10.3390/ijerph17114135
  8. Liu, Y., Zhang, Z., Han, D., Zhao, Y., Yan, X., & Cui, S. (2022). Association between environmental chemicals co-exposure and peripheral blood immune-inflammatory indicators. Frontiers in Public Health, 10, 980987. https://doi.org/10.3389/fpubh.2022.980987
  9. FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., LUCA, M. D., OTTAVIANI, E., & BENEDICTIS, G. D. (2000). Inflamm‐aging: An Evolutionary Perspective on Immunosenescence. Annals of the New York Academy of Sciences, 908(1), 244–254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x
  10. Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023). Chronic inflammation and the hallmarks of aging. Molecular Metabolism, 74, 101755. https://doi.org/10.1016/j.molmet.2023.101755
  11. Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. International Journal of Molecular Sciences, 20(13), 3328. https://doi.org/10.3390/ijms20133328
  12. Amjad, S., Nisar, S., Bhat, A. A., Shah, A. R., Frenneaux, M. P., Fakhro, K., Haris, M., Reddy, R., Patay, Z., Baur, J., & Bagga, P. (2021). Role of NAD+ in regulating cellular and metabolic signaling pathways. Molecular Metabolism, 49, 101195. https://doi.org/10.1016/j.molmet.2021.101195
  13. Fang, J., Chen, W., Hou, P., Liu, Z., Zuo, M., Liu, S., Feng, C., Han, Y., Li, P., Shi, Y., & Shao, C. (2023). NAD+ metabolism-based immunoregulation and therapeutic potential. Cell & Bioscience, 13(1), 81. https://doi.org/10.1186/s13578-023-01031-5
  14. Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., Wong, H.-S., Gibbs, E., Iyer, S. S., Basisty, N., Wu, Q., Kim, I.-J., Silva, E., Vitangcol, K., Shin, K.-O., … Verdin, E. (2020). Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nature Metabolism, 2(11), 1265–1283. https://doi.org/10.1038/s42255-020-00305-3
  15. Zeidler, J. D., Hogan, K. A., Agorrody, G., Peclat, T. R., Kashyap, S., Kanamori, K. S., Gomez, L. S., Mazdeh, D. Z., Warner, G. M., Thompson, K. L., Chini, C. C. S., & Chini, E. N. (2022). The CD38 glycohydrolase and the NAD sink: implications for pathological conditions. American Journal of Physiology-Cell Physiology, 322(3), C521–C545. https://doi.org/10.1152/ajpcell.00451.2021
  16. Murata, M. M., Kong, X., Moncada, E., Chen, Y., Imamura, H., Wang, P., Berns, M. W., Yokomori, K., & Digman, M. A. (2019). NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival. Molecular Biology of the Cell, 30(20), 2584–2597. https://doi.org/10.1091/mbc.e18-10-0650
  17. Imai, S., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002
  18. Rad, E. Y., Saboori, S., Tammam, J., Thondre, P. S., & Coe, S. (2024). The effect of niacin on inflammatory markers and adipokines: a systematic review and meta-analysis of interventional studies. European Journal of Nutrition, 63(6), 2011–2024. https://doi.org/10.1007/s00394-024-03425-8
  19. Yang, D.-L., Chao, K.-C., Yang, H.-T., Chen, K.-H., Dewi, L., Condello, G., Ye, M., Nicholls, A., Liao, Y.-C., Huang, C.-Y., & Kuo, C.-H. (2026). Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise. Journal of the International Society of Sports Nutrition, 23(1), 2632284. https://doi.org/10.1080/15502783.2026.2632284
  20. Traba, J., Kwarteng-Siaw, M., Okoli, T. C., Li, J., Huffstutler, R. D., Bray, A., Waclawiw, M. A., Han, K., Pelletier, M., Sauve, A. A., Siegel, R. M., & Sack, M. N. (2015). Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. Journal of Clinical Investigation, 125(12), 4592–4600. https://doi.org/10.1172/jci83260
  21. Zhou, B., Wang, D. D., Qiu, Y., Airhart, S., Liu, Y., Stempien-Otero, A., O’Brien, K. D., & Tian., R. (2020). Boosting NAD Level Suppresses Inflammatory Activation of PBMC in Heart Failure. Journal of Clinical Investigation, 130(11), 6054–6063. https://doi.org/10.1172/jci138538
  22. Remie, C. M., Roumans, K. H., Moonen, M. P., Connell, N. J., Havekes, B., Mevenkamp, J., Lindeboom, L., Wit, V. H. de, Weijer, T. van de, Aarts, S. A., Lutgens, E., Schomakers, B. V., Elfrink, H. L., Zapata-Pérez, R., Houtkooper, R. H., Auwerx, J., Hoeks, J., Schrauwen-Hinderling, V. B., Phielix, E., & Schrauwen, P. (2020). Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. The American Journal of Clinical Nutrition, 112(2), 413–426. https://doi.org/10.1093/ajcn/nqaa072
  23. Wu, J., Singh, K., Lin, A., Meadows, A. M., Wu, K., Shing, V., Bley, M., Hassanzadeh, S., Huffstutler, R. D., Schmidt, M. S., Blanco, L. P., Tian, R., Brenner, C., Pirooznia, M., Kaplan, M. J., & Sack, M. N. (2022). Boosting NAD+ blunts toll-like receptor-4 induced type-I interferon in control and systemic lupus erythematosus monocytes. Journal of Clinical Investigation, 132(5), e139828. https://doi.org/10.1172/jci139828
  24. Han, K., Klein, R. J., Recupero, T. C., Russo, A. C., Sharma, R., K, A., Gupta, Hassanzadeh, S., Huffstutler, R., Dagur, P. K., Fisk, B., Redekar, N. R., & Sack, M. N. (2026). NAD+ augmentation by nicotinamide riboside engages SLIT2/ROBO1 signaling to attenuate Th17 inflammation in psoriasis. JCI Insight. https://doi.org/10.1172/jci.insight.203826
  25. Brakedal, B., Dölle, C., Riemer, F., Ma, Y., Nido, G. S., Skeie, G. O., Craven, A. R., Schwarzlmüller, T., Brekke, N., Diab, J., Sverkeli, L., Skjeie, V., Varhaug, K., Tysnes, O.-B., Peng, S., Haugarvoll, K., Ziegler, M., Grüner, R., Eidelberg, D., & Tzoulis, C. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism, 34(3), 396-407.e6. https://doi.org/10.1016/j.cmet.2022.02.001
  26. Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023). Inflammation and aging: signaling pathways and intervention therapies. Signal Transduction and Targeted Therapy, 8(1), 239. https://doi.org/10.1038/s41392-023-01502-8