Clinical Nutrition · Oct 10, 2026

Zinc supplementation counteracts the age-related impairment of interferon-α response by reconstituting basal interferon Regulatory factor 3 levels

By Schulz MT, Schoofs H, Jakobs J et al.

BACKGROUND & AIMS: Immunosenescence increases the risk of infectious diseases in the aged population. A health issue partially caused by a reduced interferon (IFN)-α response. With zinc playing a crucial role in antiviral immunity and zinc-deficiency being highly prevalent in the elderly, this study examined the association between the age-related decline in IFN-α production and zinc status. The aim of this study was to compare the IFN-α response of young controls to geriatric patients stratified by their zinc status, to examine the zinc dependency of the transcription factor Interferon Regulatory Factor (IRF)3 and to investigate whether short-term zinc supplementation of zinc-deficient elderly can restore the antiviral immune competence. METHODS: 41 young healthy controls (YC) and 75 geriatric patients (O; old) were included. The geriatric cohort was divided into zinc-adequate (O-ZA) and zinc-deficient (O-ZD) subgroups based on the measured serum zinc and dietary zinc intake assessed via a food-questionnaire. Whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated with Newcastle Disease Virus (NDV) or Sendai Virus (SDV) for 24 h. The subsequent production of IFN-α was measured by ELISA. In addition, basal protein expression of IRF3 was analysed by Western blot. Patients, identified as zinc-deficient, were supplemented with 10 mg of elemental zinc for about 7 days, followed by repeating the measurements. RESULTS: 71% of the geriatric cohort was identified as zinc-deficient. Although the total geriatric group produced significantly less IFN-α compared to the young controls, the zinc-adequate seniors produced significantly higher levels of IFN-α than the zinc-deficient subgroup. Consistent with these findings, a significantly reduced expression of IRF3 was observed in zinc-deficient patients. Furthermore, a significant positive correlation between zinc status, IRF3 expression and IFN-α production was found. In patients that responded to the supplementation with an increase in serum zinc, this supplementation could also restore the IFN-α production to levels comparable to the zinc-adequate seniors. CONCLUSIONS: The findings indicate that the reduced IFN-α response is not an inevitable part of aging. By reducing the basal availability of IRF3, zinc deficiency builds a molecular barrier that limits the cellular capacity for IFN-α production. However, short-term zinc supplementation can counteract this limitation. Hence, routine assessment and correction of zinc status should be integrated into geriatric care to enhance immune resilience in the aging population.

doi.org/10.1016/j.clnu.2026.106818 Open access PubMed 42913357 Interventions