Data Sheet 2_Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.pdf

BackgroundImmunosenescence is an important factor in the impaired immune response in older adults and plays a significant role in the development of biological aging. Targeting immunosenescence could present a novel pharmacological approach to mitigating aging and age-related diseases. We aimed to investigate the effect of N-acetylcysteine (NAC) and vitamin D (Vit-D) on the senescence of peripheral blood mononuclear cells (PBMCs).
MethodThis randomized clinical trial was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either (A) 1000 IU of Vit-D daily (D1) (B), 1000 IU of Vit-D plus 600 mg of NAC daily (D1N) (C), 5000 IU of Vit-D daily (D5), or (D) 5000 IU of Vit-D plus 600 mg of NAC daily (D5N) for 8 weeks. Senescence-associated beta-galactosidase (SA-β-gal) staining, expression of senescence-related genes, and serum inflammatory factors were measured at baseline and after 8 weeks.
ResultsAfter the intervention, supplementation with D5N and D5 significantly downregulated p16, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression and decreased SA-β-gal activity compared to the D1 group. Additionally, co-administration of NAC with 1000 IU of Vit-D significantly downregulated p16 transcripts in PBMCs compared to Vit-D 1000 IU alone. No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR) after the intervention.
ConclusionsThe loading dose of Vit-D significantly attenuates senescence in PBMCs of older adults. However, co-administration of NAC with both the standard and loading doses of Vit-D further enhances these beneficial effects.
Clinical trial registrationhttps://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.

背景 免疫衰老（immunosenescence）是老年人免疫应答受损的重要影响因素，在生物性衰老的发生发展中发挥关键作用。靶向干预免疫衰老人群，有望为延缓衰老及年龄相关疾病提供全新的药理学策略。本研究旨在探讨N-乙酰半胱氨酸（N-acetylcysteine, NAC）与维生素D（vitamin D, Vit-D）对外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）衰老的影响。
方法 本随机临床试验纳入维生素D缺乏的老年人群。符合入组标准的受试者被随机分配至4组，分别接受为期8周的干预：(A) 每日补充1000 IU维生素D（D1组）；(B) 每日补充1000 IU维生素D联合600 mg N-乙酰半胱氨酸（D1N组）；(C) 每日补充5000 IU维生素D（D5组）；(D) 每日补充5000 IU维生素D联合600 mg N-乙酰半胱氨酸（D5N组）。分别于基线及干预8周后检测衰老相关β-半乳糖苷酶（senescence-associated beta-galactosidase, SA-β-gal）染色、衰老相关基因表达水平及血清炎症因子水平。
结果 干预结束后，与D1组相比，D5N组与D5组的p16基因、白细胞介素-6（interleukin-6, IL-6）及肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）表达水平显著下调，且SA-β-gal活性降低。此外，与单独补充1000 IU维生素D组相比，联合应用N-乙酰半胱氨酸与1000 IU维生素D可显著下调PBMCs中p16基因的转录水平。干预后各组血清IL-6、C反应蛋白（C-reactive protein, CRP）及中性粒细胞与淋巴细胞比值（neutrophil-to-lymphocyte ratio, NLR）均无显著差异。
结论 负荷剂量维生素D可显著延缓老年人PBMCs的衰老进程。然而，联合应用N-乙酰半胱氨酸与标准剂量或负荷剂量维生素D，可进一步增强上述有益效应。
临床试验注册 注册链接：https://irct.behdasht.gov.ir，注册编号：IRCT20230508058120N1。