自然死亡的主要原因包括心血管疾病、癌症和呼吸系统疾病。导致疾病的因素包括遗传倾向、衰老、压力、慢性炎症、环境因素、自噬能力下降以及内分泌异常（包括维生素 D 水平不足）。维生素 D 补充剂治疗心血管疾病的临床结果尚无定论，这表明需要无偏见地确定因果关系。在这项研究中，我们采用了能够分析大量不同数据集的谱聚类方法，以检查维生素 D 的基因组和非基因组信号在疾病中的作用。本研究结果表明：（1）维生素 D 调节多个相互反馈环路，包括 p53、巨噬细胞自噬、一氧化氮和氧化还原信号传导； (2)这些监管方案涉及2000多种疾病。此外，维生素 D 的基因组和非基因组信号之间的平衡会影响组织稳态中巨噬细胞极化的自噬调节。这些发现让我们更深入地了解基因组和非基因组信号传导之间的相互作用如何影响维生素 D 药理学，并为提高以维生素 D 为中心的心血管疾病治疗和健康寿命的功效提供了机会。© 2024 Fliri 和 Kajiji。

Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.© 2024 Fliri and Kajiji.