Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes

Abstract

Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results.

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“…Survivorships were scored regularly and eliminated the unnatural death flies, and death flies were removed out of the cage when possible. Lifespan curves, mean lifespan (average value of all values), and maximum lifespan (average values of the last 20 dead flies) were calculated for each group of female Drosophila ( 28 ).…”

Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan

“…However, resveratrol and pterostilbene have been shown to increase lifespan only in specific preclinical models, were context-dependent, showed mixed results, and are debated [ 91 ]. Pterostilbene has been shown to improve antioxidant function and increase longevity by activating longevity-associated genes, namely SIRT2, and has varying effects in male and female Drosophila models with the same longevity-inducing results but differing mechanisms [ 92 ]. Pterostilbene exhibits an 80% increased bioavailability, compared to that of resveratrol at 20%, and possesses many of the same beneficial biologically modulating effects of resveratrol.…”