An aqueous extract of the brown alga Eisenia bicyclis extends lifespan in a sex-specific manner by interfering with the Tor-FoxO axis

Abstract

Food has a decisive influence on our health, to the extent where even lifespan can be directly affected by it. In the present work, we have examined the effects of an aqueous extract of the marine brown alga Eisenia bicyclis in terms of its potential to extend lifespan. For this purpose, we used the fruit fly Drosophila melanogaster as a model. The experiments showed that small amounts of Eisenia extract can extend lifespan by up to 40%. This effect is not only related to the median but also to the maximum lifespan. Interestingly, this life-extending effect is sex-specific, i.e. it occurs exclusively in females. Even under stressful nutritional conditions such as a high sugar diet, this effect is detectable. Mechanistic studies showed that this life-prolonging effect depends on a functional Tor and a functional FoxO signaling pathway. It can be concluded that components of the Eisenia extract prolong lifespan by interacting with the Tor-FoxO axis. This study may serve to stimulate further investigations, which on the one hand show such a life-prolonging effect also in other organisms and on the other hand identify the substances responsible for this effect. Finally, it may also encourage the increased use of arame as a health-promoting food supplement.

Keywords: Tor; alga; lifespan; sex-specific.

Figure 1

Application of Eisenia bicyclis extract (EBE) enhances lifespan in female Drosophila. Lifelong application of 0.05% EBE (red) to adult female Drosophila (w¹¹¹⁸) was compared to control flies of the same genotype (blue). The proportion of surviving animals is displayed against time (A). In (B), 0.1 % EBE was used under otherwise identical conditions. A similar analysis was performed with w¹¹¹⁸ males and 0.05% EBE was applied (red) and compared with controls (blue) (C). Female flies of the yw strain were confronted with 0.05 EBE (red and compared to matching controls (blue) (D). (n > 100 per condition). Statistical analyses were done using a log-rank test. Ns means not significant, *** means p< 0.005, **** means p<0.001.

Figure 2

Effects of Eisenia bicyclis extract of physiological parameters of female Drosophila. Application of EBE to female adult flies did not change the intake of nutrients over a 24 h period (A). The body weight was also not changed in response to EBE (B). The effects on body fat (C), on body glucose (D) and body protein (E) were quantified. Fecundity was quantified under both conditions (F). N≥10, mean values ± S.E.M. are given. Statistical analyses were performed with unpaired t-tests. Ns means not significant, ** means p< 0.01.

Figure 3

Influence of Eisenia bicyclis extracts on activity and sleep of adult female flies. Activity traces derived from a DAM-based analysis (A) of mated female flies in a 24h period. The total mean activity in a 24h period (B), the accumulated total sleep time (C), and the accumulated daytime sleep time (D) and the accumulated nighttime sleep time (E). N≥10, mean values ± S.E.M. are given (B–E). Average sleep amounts are stated as a fraction of 1. Statistical analyses were performed with unpaired t-tests. Ns means not significant, * means p< 0.05.

Figure 4

Influence of Eisenia bicyclis extracts of lifespan in response to different stressors. Lifespan of w¹¹¹⁸ females in response to starvation (A) and desiccation (B) in control flies and those subjected to 0.05 % EBE. Lifespan of W1118 females on a high-fat diet (C) and a high sugar diet (D) (n > 100 per condition). Statistical analyses were done using a log-rank test. ns means not significant, * means p<0.05, ** means p< 0.01, **** means p<0.001.

Figure 5

Mode of action of the Eisenia bicyclis extract induced lifespan prolongation. The alpha-Amylase activity of control flies and EBE treated ones (A) are displayed. Lifespan analyses of control and EBE-treated female flies of the genotypes: dSir2-deficient (B), TOR-deficient (C), and FoxO-deficient (D). Western blot analysis of samples from control flies (Co) and EBE-treated ones (EBE) of puromycin treated flies (E) and the quantification of bad intensities (F). lifespan did not increase on concentrated medium containing 0.05 % EBE, (n > 100 per condition). Protein synthesis of flies treated with 0.05 % EBE was not affected (E, F). N≥10, mean values ± S.E.M. are given (A, F). Statistical analyses were performed with unpaired t-tests. ns means not significant. (B–D, n > 100 per condition). Statistical analyses were done using a log-rank test. ns means not significant, **** means p<0.001.

Figure 6

Untargeted HPLC-MS analysis of algae extracts. Principal component analysis (PCA) (A) of algae extracts measured using the ESI+ and ESI- acquisition mode. Underlying peak areas are log10 transformed and pareto-scaled. (B, C) LC-ToF-MS intensities of 7-phloroeckol (B) and caffeic acid quinone (C). Intensities are displayed as the mean of triplicate injections (duplicate injections for Saccorhiza).