Antihypertensive Drug Rilmenidine is a Calorie Restriction Mimetic

Researchers here use nematode worms to demonstrate that a commonly used antihypertensive drug is a calorie restriction mimetic. The beneficial response to calorie restriction, resulting in improved health and longevity, evolved very early in the development of life, and the underlying mechanisms are surprisingly similar across near all species, even if the end results vary in degree. Long-lived species do not exhibit the sizable gains in life span observed in short-lived species, for example, even though the health benefits remain noteworthy. In the nematode study, the drug produces less impressive results than actual calorie restriction in this species, always the case with these compounds, but the extension of life span is the same ballpark as the results obtained using various other calorie restriction mimetic strategies and related genetic alterations in nematodes.

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,NRF2,NRF3/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.

Link: https://doi.org/10.1111/acel.13774

Comments

OT: I wonder why there is silence here on the reported breakthrough in ultrasound therapy.

Posted by: Thomas Schaefer at January 30th, 2023 8:11 AM

Hi Thomas. I've never heard of this breakthrough. Could you link the article so that we can read about it? Thank you.

Posted by: Kurt at January 31st, 2023 11:04 AM

I'm not allowed to post URLs here, but google: studyfinds Ultimate anti-aging remedy is ultrasound therapy .

Posted by: Thomas Schaefer at February 1st, 2023 8:14 AM
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