Determine the longevity impact of oxymetazoline

Determine whether oxymetazoline affects longevity and, if so, ascertain whether its action is pro-longevity by experimentally evaluating its effects on lifespan and on aging-associated gene expression patterns within the Altered intercellular communication hallmark predicted by the Systematic Hallmark-based Aging Repurposing Pipeline (SHARP).

Background

The paper introduces SHARP, a network medicine framework that identifies drugs in network proximity to hallmark-specific modules of aging and uses a transcription-based metric, pAGE, to infer whether a drug’s perturbation counters age-related expression changes. Within this framework, oxymetazoline emerged as a candidate predicted to target the Altered intercellular communication hallmark with a positive pAGE, suggesting potential pro-longevity effects.

Mechanistically, oxymetazoline targets adrenergic and serotonin receptors (ADRA1A/ADRA1B/ADRA1D and HTR1A/HTR1B/HTR1D). ADRA1A is itself a hallmark-associated gene, and the authors propose a network propagation pathway involving ACKR3 with downstream effects on NFKB1, TP53, and AKT1, culminating in a significant pAGE value. Despite these predictions, the authors explicitly note that oxymetazoline’s actual impact on longevity has not been established, motivating experimental validation.