Publications

Marianna Raczyk and Carsten Carlberg

From Sunlight to Signaling: Evolutionary Integration of Vitamin D and Sterol Metabolism

Metabolites 2026, 16(1), 74;

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics.

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Carsten Carlberg, Andreas Blüthner, Irini Schoeman-Giziakis, Annemarie Oosting, Luca Cocolin

Modulating biological aging with food-derived signals: a systems and precision nutrition perspective

npj Aging volume 11, Article number: 76 (2025)

Lifespan extension has not prevented age-related decline. We propose that diet acts as a molecular modulator of aging, influencing inflammation, the microbiome, and systemic resilience. Biological age markers and AI-powered multi-omics reveal actionable dietary targets, including food-derived signals and Nutrition Dark Matter. We highlight precision nutrition and the EIT Food Healthy Aging Think & Do Tank as pathways to align science, policy, and practice for healthy aging.

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Mariusz Jankowski, Emmi Hämäläinen, Mari Taipale, Sami Heikkinen & Carsten Carlberg

Vitamin D and lipopolysaccharide jointly induce a distinct epigenetic and transcriptional program in human monocytes

Scientific Reports volume 15, Article number: 27480 (2025)

Pathogen-associated molecular patterns such as lipopolysaccharide (LPS) mimic immune responses triggered by bacterial infections. The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], supports innate immunity, but its molecular mechanisms remain incompletely understood. We investigated epigenomic and transcriptomic changes in THP-1 monocytes that were either unprimed or primed for 24 h with 1,25(OH)2D3 or LPS, followed by a second 24-hour stimulation with 1,25(OH)2D3, LPS, or their combination. Epigenome profiling via ATAC-seq revealed that co-stimulation with 1,25(OH)2D3 and LPS induces substantially more chromatin accessibility changes than either treatment alone, with up to 81% of altered regions uniquely responsive to the combination. Motif enrichment analysis highlighted JUN/FOS transcription factors as key regulators of this synergistic response. Transcriptomic analysis via RNA-seq mirrored these findings, though fewer genes than chromatin regions were affected. Notably, under 1,25(OH)2D3-primed conditions, 331 genes exhibited synergistic expression changes upon co-treatment, meaning that their responses significantly deviates from the additive effects of the individual stimulations. This includes 264 genes previously unrecognized as vitamin D targets. Functional annotation revealed that these genes are primarily linked to monocyte and T cell differentiation, in contrast to classical vitamin D targets associated with inflammation. In conclusion, our findings provide mechanistic insight into how vitamin D modulates inflammation through epigenetic and transcriptional reprogramming.

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Tanya Tripathi, Carsten Carlberg

Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense

Frontiers in Immunology

Vitamin D3 is a vital micronutrient that can either be synthesized endogenously in the skin upon exposure to UV-B radiation or obtained through dietary sources and supplementation. One of the most ancient evolutionary roles of vitamin D is maintaining energetic and survival homeostasis, such as detoxification. However, its most well-known physiological function is regulating calcium homeostasis, which is crucial for bone mineralization. Beyond these roles, vitamin D also plays a critical part in modulating the immune system. It supports the innate immune response to infectious diseases, such as tuberculosis and COVID-19 (coronavirus disease), while also preventing overactivation of the adaptive immune system. This dual function is essential for reducing the risk of autoimmune diseases, such as multiple sclerosis, and for mitigating severe immune responses, such as those observed in critical cases of COVID-19.

Early in vivo target genes in human immune cells highlight vitamin D’s role in antioxidant defense [PDF]

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