Vitamin D 3 inhibits p38 MAPK and senescence‐associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing

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 s...

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Bibliographic Details
Published inAging cell Vol. 23; no. 4; p. e14093
Main Authors Sayegh, Souraya, Fantecelle, Carlos Henrique, Laphanuwat, Phatthamon, Subramanian, Priya, Rustin, Malcom H. A., Gomes, Daniel C. O., Akbar, Arne N., Chambers, Emma S.
Format Journal Article
LanguageEnglish
Published England 01.04.2024
Subjects
Adult
Aged
Aging
Cellular Senescence - genetics
Cholecalciferol - metabolism
Cholecalciferol - pharmacology
Fibroblasts - metabolism
Humans
Immunity
Inflammation Mediators - metabolism
p38 Mitogen-Activated Protein Kinases - metabolism
senescence
skin
ageing
SASP
p38 MAPK
vitamin D
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Summary: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.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.14093