HQ Team
January 31, 2023: Studies on animals have shown that a drug used to treat hypertension prolongs the human lifespan and slows ageing, mimicking the effects of calorific restriction.
Scientists at the University of Liverpool demonstrated the health benefits of rilmenidine and are exploring if it has other clinical applications.
“With a global ageing population, the benefits of delaying ageing, even if slightly, are immense,” Professor João Pedro Magalhães, who led the research at the University of Liverpool and is currently at the University of Birmingham.
“Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. We have shown in animals that rilmenidine can increase lifespan for the first time. We are keen to explore if rilmenidine may have other clinical applications.”
Geoscience potential
Repurposing has a vast untapped potential in translational geroscience.
The scientists 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.
The researchers went on to show that treating Caenorhabditis elegans with rilmenidine at young and older ages increases lifespan.
They also demonstrated 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.
Caenorhabditis elegans are a transparent nematode about 1 millimetre long and live in temperate soil environments.
Liver, kidney tissues
Transcriptional changes similar to caloric restriction were observed in liver and kidney tissues in mice treated with rilmenidine.
“These results reveal a geroprotective and potential caloric restriction mimetic effect by rilmenidine that warrant fresh lines of inquiry into this compound,” according to the study published in Aging Cell.
Individuals over 65 are now the fastest-growing demographic group worldwide, a fact that emblematizes the global ageing population. Even if the effect is rather small, the estimated benefits of delaying ageing are immense.
By 2030, 1 in 6 people in the world will be aged 60 years or over, according to the WHO. The share of the population aged 60 years and over will increase from 1 billion in 2020 to 1.4 billion.
By 2050, the world’s population of people aged 60 years and older will double to 2.1 billion. The number of persons aged 80 years or older is expected to triple between 2020 and 2050 to reach 426 million.
‘Population ageing’
The shift in the distribution of a country’s population towards older ages – known as population ageing – started in high-income countries. For example, 30% of Japan’s population is already over 60 years old.
Low- and middle-income countries are now experiencing the most significant change. By 2050, two-thirds of the world’s population over 60 years will live in low- and middle-income nations.
A large body of evidence has demonstrated that the ageing rate can be markedly slowed in model organisms. So far, caloric restriction is the most robust anti-ageing intervention.
However, studies of calorific restriction in humans have had mixed results, low compliance, and many side effects. Only a few compounds have been identified to mimic the beneficial effects of calorific restriction.
The scientists previously compared drug-gene signatures to the in vitro transcriptome of caloric restriction, looking for drugs with an overlapping profile.
Allantoin drug
One drug identified during this work was allantoin, which was further confirmed to extend the lifespan in Caenorhabditis elegans. Allantoin, however, did not display oral bioavailability, hindering its use in humans.
Rilmenidine administration extended the lifespan in C. elegans when commenced from early adulthood or only once the animal had aged. It decelerated the development of decrepitude without altering developmental periods.
Alongside being a clinically approved antihypertensive drug, rilmenidine improves plasma lipid and blood glucose in patients with hypertension and metabolic syndrome.
Given its contribution toward lowering blood glucose and increasing insulin sensitivity, rilmenidine may have an anti-diabetic function.
