Hypertension drug could be repurposed to delay aging, study finds

by University of Liverpool

Induced autophagy by rilmenidine perturbed polyQ aggregation. (a) Representative images of day 2 adult transgenic animals, expressing the intestinal specific autophagy reporter gene Pnhx-2::mCherry::lgg-1 showing increased autophagy, when exposed to varying concentrations of rilmenidine for 24 h compared to 1% DMSO vehicle. Arrows indicate autophagosome puncta formation. Scale bar = 20 μm. (b) The graph shows the interquartile distribution of the mean number of mCherry::LGG-1 puncta in the posterior intestine of the animals in each condition. Error bars, upper: Q3 + 1.5*IQR; minimum: Q1–1.5*IQR. **p < 0.01, *p < 0.05; one-way ANOVA followed by a Tukey’s post hoc test. (c, d) Inhibition of autophagy abrogates the prolongevity effect of rilmenidine as shown by survival curves of WT animals fed either RNAi bacteria expressing an empty vector (L4440), or lgg-1 (c) or bec-1 (d) dsRNA from day 1 adulthood in the presence or absence of 200 μM rilmenidine. Kaplan–Meir survival analysis was performed on pooled data from at least three independent trials. Groups tested by log-rank with Bonferroni correction; p < 0.05. Quantitative data and statistical analyses for the representative experiments are included in Table S1. (e) The graph depicts quantified data of Q40::YFP aggregates in body wall muscles per entire animal after treatment with differing rilmenidine concentrations for the indicated times from L1. Data represented as the pooled mean number of aggregates per animal. Error bars are ± SEM. Significance derived from two-way repeated-measures ANOVA p < 0.05. Credit: Aging Cell (2023). DOI: 10.1111/acel.13774

Researchers have found that the drug rilmenidine can extend lifespan and slow aging.

Published in Aging Cell, the findings show that animals treated with rilmenidine, currently used to treat hypertension, at young and older ages increases lifespan and improves health markers, mimicking the effects of caloric restriction.

They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.

Unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed, oral antihypertensive rilmenidine has potential for future translatability to humans as side-effects are rare and non-severe.

To date, a caloric restriction diet has been considered the most robust anti-aging intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-aging strategy.

Professor João Pedro Magalhães, who led the research while at the University of Liverpool and is now based at the University of Birmingham, said, “With a global aging population, the benefits of delaying aging, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”