Bennett, Dominic F, Goyala, Anita, Statzer, Cyril, Beckett, Charles W, Tyshkovskiy, Alexander, Gladyshev, Vadim N, Ewald, Collin Y and de Magalhaes, Joao Pedro 
ORCID: 0000-0002-6363-2465
(2023)
Rilmenidine extends lifespan and healthspan in<i> Caenorhabditis</i><i> elegans</i> via a nischarin I1-imidazoline receptor.
AGING CELL, 22 (2).
e13774-.
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Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor.pdf - Open Access published version Download (4MB) | Preview |
Abstract
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. Furthermore, 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.
| Item Type: | Article |
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| Uncontrolled Keywords: | aging, autophagy, drug repurposing, longevity, mTOR, nischarin receptor |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 May 2023 14:58 |
| Last Modified: | 17 Oct 2023 22:35 |
| DOI: | 10.1111/acel.13774 |
| Open Access URL: | https://doi.org/10.1111/acel.13774 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3170453 |
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