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 (open access) December 18, scientists showed that regular doses of ibuprofen extended the lifespan of yeast, worms and fruit flies.

Brian Kennedy, PhD, CEO of the Buck Institute, 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 “anti-aging medicines.”

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.”

Equivalent to a dozen or so human years

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.”

In C. elegans worms, ibuprofen has also been shown to suppress a phenotype associated with aging, inhibiting the deposition of amyloid β peptide, a marker for Alzheimer disease, the paper notes.

Ibuprofen is in the class of compounds known as NSAIDs — nonsteroidal anti-inflammatory drugs used for relieving pain, helping with fever and reducing inflammation.  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.

Researchers at Texas A & M University, University of Washington, and Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, Russia were also involved in the study.

The research was funded by the National Science Foundation, the National Institutes of Health (R01-AG043080; R01-AG025549), the Glenn Foundation for Medical Research, the Presidium of RAS (12-P-4-1055), and the President of Russian Federation (MD-1090.2014.4)

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

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.