Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.

Background: Immunosenescence 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). Method: This 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. Results: After the intervention, supplementation with D5N and D5 significantly downregulated Conclusions: The 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 registration: https://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.