Vitamin D3 inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing

• Published in: Aging 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
• Language: English
• Published: Hoboken John Wiley and Sons Inc 01.04.2024
• Subjects: Short Communication; Short Communications
• ISSN: 1474-9726; 1474-9718; 1474-9726
• DOI: 10.1111/acel.14093

Vitamin D3 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 D3 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 D3 supplementation shows that vitamin D3 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 D3 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.Vitamin D3 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 D3 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 D3 supplementation shows that vitamin D3 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 D3 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.