Summary: Rilmenidine, a drug commonly prescribed to help treat hypertension can help slow the effects of aging and extend lifespan, a new study reports.
Source: University of Liverpool
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 whilst 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.”
Funding: This study was undertaken by researchers from the University of Liverpool, ETH Zürich and Harvard Medical School, and funded by the Swiss National Science Foundation, LongeCity and the Biotechnology and Biological Sciences Research Council.
Rilmenidine extends lifespan and healthspan in C. elegans via a nischarin I1- imidazoline receptor
Repurposing drugs capable of extending lifespan and health span has a huge untapped potential in translational geroscience.
Here, we searched for known compounds that elicit a similar gene expression signature to caloric restriction and identified rilmenidine, an I1-imidazoline receptor agonist and prescription medication for the treatment of hypertension.
We then show that treating Caenorhabditis elegans with rilmenidine at young and older ages increases lifespan. We also demonstrate that the stress-resilience, health span, and lifespan benefits of rilmenidine treatment in C. elegans are mediated by the I1-imidazoline receptor nish-1, implicating this receptor as a potential longevity target.
Consistent with the shared caloric-restriction-mimicking gene signature, supplementing rilmenidine to calorically restricted C. elegans, genetic reduction of TORC1 function, or rapamycin treatment did not further increase lifespan. The rilmenidine-induced longevity required the transcription factors FOXO/DAF-16 and NRF1,2,3/SKN-1. F
urthermore, we find that autophagy, but not AMPK signaling, was needed for rilmenidine-induced longevity. Moreover, transcriptional changes similar to caloric restriction were observed in liver and kidney tissues in mice treated with rilmenidine.
Together, these results reveal a geroprotective and potential caloric restriction mimetic effect by rilmenidine that warrant fresh lines of inquiry into this compound.