Long live the …yeast. Ibuprofen to increase lifespan in lower eukaryotes

What if the secret to staying young was in your medicine cabinet all along?

Ibuprofen belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs) and is commonly used as an analgesic, antipyretic and anti-inflammatory agent. Like aspirin, ibuprofen acts by inhibiting cyclooxygenase, which is a key enzyme in the pathway to synthesize prostaglandins, prostacyclins and thromboxanes. These lipid-based signalling molecules act locally to regulate inflammation, blood pressure, blot clotting and other related processes.

In the first study aiming to analyze the effect of ibuprofen on lifespan, He et al. show that administration of physiologically relevant doses of ibuprofen enhanced longevity in the three model organisms tested: baker’s yeast, the roundworm and the fruit fly.

The paper, published in PLOS Genetics, cites previous reports correlating long-term ibuprofen use with a decreased risk of developing Alzheimer’s and Parkinson’s diseases, an effect believed to be independent of its anti-inflammatory action.

Based on these studies, the authors hypothesized that the neuroprotective function of ibuprofen stems from a general role of this drug in anti-aging. Their results indicate a lifespan increase of 10-17% upon ibuprofen treatment that is independent of the cyclooxygenase-inhibitory function, at least in yeast and worms. However, the positive effect on longevity was not seen in male flies, which responded differently to ibuprofen than female flies, and showed a decreased lifespan compared to their untreated counterparts.

Focusing on yeast, the researchers suggest that the target of ibuprofen is Tat2p, a transmembrane protein involved in the import of tryptophan and of other aromatic amino acids. In contrast to yeast, which derive tryptophan both from biosynthesis and external sources, humans cannot synthesize tryptophan and rely entirely on extracellular uptake. Therefore, the authors propose that import of aromatic amino acids might become an important target in anti-aging therapy, an idea supported by data showing that knockdown of aromatic amino acid transporters in C.elegans increases lifespan.

 

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