We recently published that phycocyanin, a phycobiliprotein which accounts for up to 20% of Arthrospira platensis dry weight, has a powerful anti-aging effect, greatly extending the chronological life span (CLS) of yeast cells grown in synthetic-defined medium, both under caloric restriction (CR) conditions (0.2% glucose) or under non-CR conditions (2% glucose). In this study, to explore the molecular mechanisms underlying the effects of phycocyanin, we investigated its impact on key signaling pathways involved in aging. Specifically, we performed CLS experiments using ras2Δ and snf1Δ yeast mutants. The Snf1 pathway is known to promote longevity (anti-aging), whereas the Ras2/PKA pathway accelerates aging (pro-aging). We show that, while in the snf1Δ mutant the anti-aging effect of phycocyanin was still evident, in the ras2Δ mutant, phycocyanin did not appear to exert any anti-aging activity, leading us to hypothesize that the Ras2/PKA pathway may be essential to mediate the anti-aging effect of phycocyanin. To evaluate the activity of phycocyanin under different nutritional conditions, we performed the CLS experiment in a YPDA-rich medium. We show that in this medium, phycocyanin accelerated the chronological aging process of yeast cells, greatly decreasing the CLS, both when glucose was present at low (0.2%) or at high (2%) concentration. Our data suggest that Saccharomyces cerevisiae could serve as a model not only to investigate the anti-aging properties and targets of phycocyanin, but also its potential side effects, which are possibly present in higher eukaryotes under certain conditions.

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Cassamagnaghi D, Citterio S, Martegani E, Colombo S

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