Vitamin <scp> D <sub>3</sub> </scp> inhibits p38 <scp>MAPK</scp> and senescence‐associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing
Souraya Sayegh, Carlos Henrique Fantecelle, Phatthamon Laphanuwat, Priya Subramanian, M.H.A. Rustin, Daniel Cláudio Oliveira Gomes, Arne N. Akbar, Emma S. Chambers
Abstract
Abstract Vitamin D 3 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 3 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 3 supplementation shows that vitamin D 3 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 3 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.