Ibuprofen extended lifespan an average of 15 percent in model organisms

Ibuprofen, a common over-the-counter drug used to relieve pain and fever, could hold the keys to a longer healthier life, according to a study by researchers at the Buck Institute for Research on Aging. Publishing in PLoS Genetics on December 18th, scientists showed that regular doses of ibuprofen extended the lifespan of yeast, worms and fruit flies.

“There is a lot to be excited about,” said Brian Kennedy, PhD, CEO of the Buck Institute, who said treatments, given at doses comparable to those used in humans, extended lifespan an average of 15 percent in the model organisms. “Not only did all the species live longer, but the treated flies and worms appeared more healthy,” he said. “The research shows that ibuprofen impacts a process not yet implicated in aging, giving us a new way to study and understand the aging process.” But most importantly, Kennedy said the study opens the door for a new exploration of so-called “anti-aging medicines.” “Ibuprofen is a relatively safe drug, found in most people’s medicine cabinets,” he said. “There is every reason to believe there are other existing treatments that can impact healthspan and we need to be studying them.”

Ibuprofen inhibits tryptophan import, reduces intracellular tryptophan levels and does not extend RLS in the absence of tryptophan permeases.

PLOS Genetics – Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

The work was the result of a collaboration between the Buck Institute and Texas A & M’s Agrilife program. Michael Polymenis, PhD, an AgriLife Research biochemist started the work in baker’s yeast and then moved it into worms and flies. Polymenis, who also is a professor in the biochemistry and biophysics department at Texas A&M University, said the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism. Tryptophan is essential for humans, who get it from protein sources in the diet. “We are not sure why this works, but it’s worth exploring further. This study was a proof of principle, to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms,” he said. “Therefore, it should be possible to find others like ibuprofen with even better ability to extend lifespan, with the aim of adding healthy years of life in people.”

“Dr. Polymenis approached me with this idea of seeing how his cell cycle analysis corresponded with our aging studies,” said Kennedy. “He had identified some drugs that had some really unique properties, and we wanted to know if they might affect aging, so we did those studies in our lab,” he said. “The Buck Institute is interested in finding out why people get sick when they get old. We think that by understanding those processes, we can intervene and find ways to extend human healthspan to keep people healthier longer to slow down aging. That’s our ultimate goal.”

Ibuprofen is in the class of compounds known as NSAID’s – nonsteroidal anti-inflammatory drugs used for relieving pain, helping with fever and reducing inflammation. It was created in the early 1960’s in England and was first made available by prescription and then, after widespread use, became available over-the-counter throughout the world in the 1980s. The World Health Organization includes ibuprofen on their “List of Essential Medications” needed in a basic health system. Although deemed relatively safe and commonly used, ibuprofen can have adverse side effects, particularly in the gastrointestinal tract and the liver at high doses.

Chong He, PhD, a postdoctoral fellow at the Buck Institute and lead author on the paper, said the extended lifespan in the model organisms would be the equivalent to another dozen or so years of healthy living in humans. “Our preliminary data in the worms showed that ibuprofen also extended their healthspan,” she said. “Healthy worms tend to thrash a lot and the treated worms thrashed much longer than would be normally expected. As they aged, they also swallowed food much faster than expected.”

Abstract

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.

Ibuprofen extends the lifespan of C. elegans worms: survival curves shown here are for worms treated with ibuprofen at a dose of 0.1 mM (red) compared to experiment-matched untreated (credit: Chong He et al./PLOS Genetics)

Author Summary

Aging is the greatest risk factor for many diseases, which together account for the majority of global deaths and healthcare costs. Here we show that the common drug ibuprofen increases the lifespan of yeast, worms and flies, indicative of conserved longevity effects. In budding yeast, an excellent model of cellular longevity mechanisms, ibuprofen’s pro-longevity action is independent of its known anti-inflammatory role. We show that the critical function of ibuprofen in longevity is to inhibit the uptake of aromatic amino acids, by destabilizing the high-affinity tryptophan permease. We further show that ibuprofen alters cell cycle progression. Mirroring the effects of ibuprofen, we found that most yeast long-lived mutants were also similarly affected in cell cycle progression. These findings identify a safe drug that extends the lifespan of divergent organisms and reveal fundamental cellular properties associated with longevity.

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