# Zinc Supplementation Partially Reconstitutes Impaired Interferon-γ Production in the Elderly

**Authors:** Krisztina Olah, Johanna Zenk, Jana Jakobs, Thea Laurentius, Leo Cornelius Bollheimer, Lothar Rink

PMC · DOI: 10.3390/ijms27021039 · 2026-01-20

## TL;DR

Zinc supplementation in elderly individuals partially restores interferon-γ production, which is often impaired with age.

## Contribution

The study demonstrates that zinc supplementation can improve immune function in the elderly, particularly in those with zinc deficiency.

## Key findings

- Elderly participants had lower zinc status and IFN-γ levels compared to young adults.
- Zinc supplementation increased serum zinc and IFN-γ production in zinc-deficient elderly individuals.
- PPI use among the elderly was associated with zinc deficiency and improved responses to zinc supplementation.

## Abstract

Aging impacts immunity, zinc status, and overall health, with these factors being closely interconnected. Zinc is known to modulate protein expression and cytokine production, with new molecular mechanisms continuing to be identified. ZIP8 facilitates IFN-γ production by increasing the intracellular zinc levels; how zinc status in humans affects ZIP8 expression remains unclear. We assessed serum zinc, dietary zinc intake, proton pump inhibitor (PPI) use, phytohemagglutinin (PHA)-stimulated IFN-γ production, and ZIP8 protein expression in elderly hospitalized patients and young healthy controls. Compared to young adults, elderly participants exhibited lower zinc status and IFN-γ levels, with PPI use among the elderly correlating with zinc deficiency. Zinc-deficient elderly participants received zinc aspartate supplementation for approximately 7 days, resulting in increased serum zinc levels, IFN-γ production, and a trend toward increased ZIP8 expression; in participants taking PPIs, this increase reached statistical significance. Although we found no clear correlation between ZIP8 expression and zinc status, the observed response to supplementation warrants further investigation. These findings reinforce the relevance of zinc supplementation in the elderly, although further studies are needed to elucidate the precise mechanisms linking zinc status to IFN-γ production, particularly regarding the role of ZIP8 expression levels.

## Linked entities

- **Proteins:** SLC39A8 (solute carrier family 39 member 8), IFNG (interferon gamma)
- **Chemicals:** zinc (PubChem CID 23994), zinc aspartate (PubChem CID 56841018)

## Full-text entities

- **Genes:** SLC39A8 (solute carrier family 39 member 8) [NCBI Gene 64116] {aka BIGM103, CDG2N, LZT-Hs6, PP3105, ZIP8}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** Zinc (MESH:C564286)
- **Chemicals:** zinc aspartate (MESH:C000629498), Zinc (MESH:D015032)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12842025/full.md

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Source: https://tomesphere.com/paper/PMC12842025