Vitamin D<sub>3</sub> inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38287646.
- Also identified by DOI 10.1111/acel.14093 and PMC identifier 11019144.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Vitamin D<sub>3</sub> replacement in older insufficient adults significantly improves their antigen-specific varicella zoster virus (VZV) cutaneous immunity. However, the mechanisms involved in this enhancement of cutaneous immunity are not known. Here, we show for the first time that vitamin D<sub>3</sub> blocks the senescence-associated secretory phenotype (SASP) production by senescent fibroblasts by partially inhibiting the p38 MAPK pathway. Furthermore, transcriptomic analysis of skin biopsies from older subjects after vitamin D<sub>3</sub> supplementation shows that vitamin D<sub>3</sub> inhibits the same inflammatory pathways in response to saline as the specific p38 inhibitor, losmapimod, which also enhances immunity in the skin of older subjects. Vitamin D<sub>3</sub> supplementation therefore may enhance immunity during ageing in part by blocking p38 MAPK signalling and in turn inhibit SASP production from senescent cells in vivo.
Medical subject headings
- Cellular Senescence
- Cholecalciferol