Abstract
Orthostatic hypotension is a sharp decrease in blood pressure when an individual transitions from a supine to an upright position. OH affects at least 30% of older adults. It is attributed to the dysfunction of the autonomic innervation and decreased vascular bed capacity. Genomic (n = 2526), methylomic (n = 910), and transcriptomic (n = 391) data from centenarians aged 90 years and older were used to examine molecular and genetic factors for OH. No statistically significant genetic predictors of OH were identified. However, the study revealed numerous epigenetic markers of OH indicative of general aging, such as DNA hypomethylation. The predictive DNA methylation-based model for orthostatic hypotension demonstrated an average accuracy of 79%. The transcriptome analyses highlighted associations between OH and inflammation pathways, as well as other age-related biological processes. Integrated omics and clinical data have identified six key mechanisms associated with orthostatic hypotension: metabolic dysregulation, impaired muscle tone, altered cell proliferation, inflammation, humoral regulation, and neural regulation.