Next Article in Journal
Functional Properties, Rheological Characteristics, Simulated Digestion, and Fermentation by Human Fecal Microbiota of Polysaccharide from Morchella importuna
Previous Article in Journal
Total Polyphenol Contents and Mineral Profiles in Commercial Wellness Herbal Infusions: Evaluation of the Differences between Two Preparation Methods
Previous Article in Special Issue
Nutritional Barriers to the Adherence to the Mediterranean Diet in Non-Mediterranean Populations
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Foods
Volume 13
Issue 13
10.3390/foods13132146
foods-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance

by
Morgane Carrara
1,*,
Myriam Richaud
2,*,
Pierre Cuq
2,
Simon Galas
2,† and
Delphine Margout-Jantac
1,†
1
Qualisud, Université de Montpellier, Avignon Université, CIRAD, Institut Agro, IRD, Université de La Réunion, 34093 Montpellier, France
2
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Université de Montpellier, 34090 Montpellier, France
*
Authors to whom correspondence should be addressed.
†
These authors should be considered as co-last authors.
Foods 2024, 13(13), 2146; https://doi.org/10.3390/foods13132146
Submission received: 7 June 2024 / Revised: 1 July 2024 / Accepted: 4 July 2024 / Published: 5 July 2024
(This article belongs to the Special Issue Mediterranean Diet: Promoting Health and Sustainability)
Browse Figures
Versions Notes

Abstract

:
Oleacein, a bioactive compound of olive oil and olive mill wastewater, has one of the strongest antioxidant activities among olive phenolics. However, few reports explore the in vivo antioxidant activity of oleacein, with no clear identification of the biological pathway involved. Earlier studies have demonstrated a link between stress resistance, such as oxidative stress, and longevity. This study presents the effects of oleacein on Caenorhabditis elegans mean lifespan and stress resistance. A significant lifespan extension was observed with an increase of 20% mean lifespan at 5 µg/mL with a hormetic-like dose-dependent effect. DAF-16 and SIR-2.1 were involved in the effects of oleacein on the longevity of C. elegans, while the DAF-2 receptor was not involved. This study also shows the capacity of oleacein to significantly enhance C. elegans resistance to oxidative and thermal stress and allows a better understanding of the positive effects of olive phenolics on health.

1. Introduction

Extra virgin olive oil (OO) comprises up to 36 phenolic compounds [1,2]; they have been associated with various health benefits [3,4], such as their antioxidant [5,6,7] and anti-inflammatory [8,9,10] activities, both in vitro and in vivo. Several studies also show that the consumption of OO phenolics may help to prevent cardiovascular, metabolic, or age-related diseases [11,12,13,14], and promote healthy aging [15,16]. In consequence, the consumption of OO is believed to be of great importance for the benefits of the Mediterranean diet [17]. Olive mill wastewater (OMW), an aqueous polluting waste generated during OO production, contains 98% of available olive phenolics [18], making it an interesting source of these compounds. Hydroxytyrosol is the most studied phenolic compound in OO and OMW for its antioxidant properties [19,20,21]. Oleacein (the dialdehydic form of elenolic acid conjugated with 3, 4-(dihydroxyphenyl)ethanol (3, 4-DHPEA-EDA)), another phenolic compound found in OO and OMW (Figure 1), has been the subject of fewer studies but has been shown to have one of the strongest in vitro antioxidant activities among olive phenolics [22,23,24,25]. Only a few studies on the in vivo testing of oleacein antioxidant activity are reported, with no clear identification of the biological pathways involved [26,27], although Nikou et al. suspect a contribution of the Ins/IGF-dependent pathway.
Lifespan is regulated by signaling pathways that are conserved from yeast to humans [28,29]. Some of the most widely studied are target of rapamycin (mTOR) signaling [30], nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins [31], and insulin/insulin-like growth factor 1 (IGF-1) regulatory pathways [28]. The roundworm Caenorhabditis elegans (C. elegans) possesses all of these regulatory pathways [28]. Because of its short lifespan, and readily available molecular tools and mutant strains [32], C. elegans is a suitable model for drug screening [33,34]. Previous reports highlighted the positive effects of phenolic compounds on the lifespan of C. elegans [35,36,37]. For example, Brunetti et al. previously demonstrated the ability of hydroxytyrosol to increase C. elegans mean lifespan by 14% at 250 µg/mL [38].
It has been reported that some phenolic compounds may induce a hormetic response [39,40,41]. Hormesis is characterized by a moderate and non-permanent stress that induces a beneficial effect at low doses and a deleterious effect at high doses and is considered an adaptive response [42,43]. More precisely, hormetic compounds are a source of stress and at low doses trigger innate overcompensation with an overall positive effect. At higher doses, this stress overwhelms defense mechanisms, explaining the observed negative effect [44]. Previous reports have shown that the hormesis function is absent in C. elegans mutations in the Daf-16 C. elegans gene [45,46]. The Daf-16 gene encodes an ortholog of the human FOXO family of transcription factors, and its genetic targets include, among others, reactive oxygen species (ROS) scavengers such as Sod-3 (superoxide dismutase) or gene-encoding chaperones such as Hsp-16.2 (heat shock protein) [47,48]. Activation/inhibition processes of the DAF-16 transcription factor are regulated by molecular pathways such as the Daf-2 (Ins/IGF)-dependent signaling pathway. Downregulation of the Daf-2 (Ins/IGF)-dependent signaling pathway leads to activation of DAF-16, resulting in a twofold extension of C. elegans lifespan [49,50]. The C. elegans Sir-2.1 gene is an ortholog of mammalian SIRT1 that belongs to the Sir-2 family of NAD+-dependent protein deacetylase-encoding genes. The deacetylase encoded by the Sir-2.1 gene can extend C. elegans lifespan via the DAF-16 transcription factor [51], notably when activated by oxidative stress [52,53].
In this manuscript, we show for the first time that oleacein can promote healthy aging in an in vivo model of C. elegans by promoting its stress resistance and extending its lifespan expectancy. We also identify C. elegans genes involved in its mechanism of action.

2. Materials and Methods

Reagents and Chemicals
HPLC-MS-grade methanol and water were purchased from Carlo-Erba reagents (Carlo-Erba reagents, Val-de-Reuil, France). DMSO was purchased from Sigma-Aldrich (Sigma-Aldrich/Merck, Darmstadt, Germany). Oleacein was purchased from Toronto Research Chemicals (Toronto Research Chemicals, Toronto, ON, Canada, ref. O524550) and was dissolved in DMSO at 15 g/L and stored at −20 °C until use. The compound 5-fluorodeoxyuridine (FUdR) was purchased from Sigma-Aldrich (Sigma-Aldrich/Merck, Darmstadt, Germany) and was dissolved in water at 0.4 M and stored at −20 °C until use.
Oleacein stability in experimental media
S-base medium [54] with oleacein at 5 or 20 µg/mL was stored in the dark at 20 °C and regularly analyzed for up to 70 days. Oleacein was quantified by reverse-phase liquid chromatography (Ultimate 3000, Thermo Scientific, Waltham, MA, USA) coupled to quadripole mass spectrometry (ISQ EC, Thermo Scientific) and ESI in negative ion mode. Mobile phases were MeOH—0.001% formic acid (A) and water—0.001% formic acid (B) delivered at 0.4 mL/min with linear gradient elution across a biphenyl column at 40 °C. The gradient program was 0–2 min, 75% B; 2–10 min, 75–45% B; 10–13 min, 45% B; 13–14 min 45–0% B; 14–15 min 0% B; 15–16 min 0–75% B; and 16–20 min 75% B. The injection volume was 5 µL, and analyses were carried out in triplicate.
Worm Strains
The N2 Bristol strain was used as a wild-type genetic background. The following mutations were used in this study: GR1307 daf-16 (mgDf50); TJ356 daf-16::GFP (zls356 [daf-16p::daf-16a/b::GFP + rol-6(su1006)]); CB1370 daf-2 (e1370); and VC199 sir-2.1 (ok434), GC363 Bacteria E. coli HT115(DE3). All strains were provided by the CGC (Caenorhabditis Genetic Center—University of Minnesota), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Wild-type and mutant strains of C. elegans strains were grown on NGM lite® plates (6 mm width) with Escherichia coli bacteria as a food source at 20 °C [55].
Lifespan assays
All lifespan assays were carried out as follows:
C. elegans synchronized L4 larvae were placed in an ELISA 96 plate previously filled with S-base medium, with FUdR at 400 µM to avoid offspring, and heat-killed E. coli (HT115) as a food source. Increasing concentrations of oleacein or DMSO-only (solvent control) were added to the wells. Medium not supplemented with either oleacein or DMSO was used as an S-base control. These controls were used to determine whether DMSO alone has a significant impact on the lifespan of C. elegans.
The number of live nematodes were counted daily until they no longer responded to light touching with a platinum wire. Those killed by accidental manipulation were counted as censored data. XLSTAT-life statistical software v. 2021.1.1 (Addinsoft, New York, NY, USA) was used to plot survival data by the Kaplan–Meier method and differences between survival curves were calculated using the Log Rank test at a 95% confidence interval. All experiments were carried out at least three times with 50 individuals per modality.
DAF-16::GFP cellular localization
Synchronized TJ356 L4 larvae expressing the DAF-16::GFP fusion protein were placed in 15 mL falcon™ tubes filled with S-base containing 400 µM FUdR to avoid offspring, and heat-killed E. coli HT115 as a food source. Media were supplemented with 5 µg/mL oleacein or DMSO as a solvent control. The tubes were incubated for 3 days at 20 °C before examination by fluorescence microscopy (LEICA M205 FCA). Subcellular DAF-16::GFP localization for each nematode was classified as “cytosolic”, “intermediate”, or “nuclear”. The experiment was carried out three times with at least 150 nematodes per modality.
Resistance to heat-shock stress
Synchronized N2 L4 larvae were prepared as per the previous section. Following three days’ incubation at 20 °C, they were placed in a water bath at 35 °C to subject them to heat stress. After five hours under these conditions, the nematodes were left in medium at 20 °C overnight and then transferred to an NGM plate. Nematodes that did not respond to light touching with a platinum wire were noted as dead. The experiment was carried out three times with at least 150 individuals per modality.
Resistance to oxidative stress
The nematodes were prepared as per the two previous sections and incubated for three days at 20 °C. To remove oleacein, the samples were rinsed three times with S-base, and then incubated with 0.6 M hydrogen peroxide for 30 min to subject them to oxidative stress. The hydrogen peroxide was removed by rinsing three times with S-base. The nematodes were left in medium at 20 °C overnight and then transferred to an NGM plate. Those that did not respond to light touching with a platinum wire were noted as dead. The experiment was carried out three times with at least 150 individuals per modality.

3. Results

3.1. Oleacein Stability during Lifespan Trials in C. elegans

Oleacein stability was monitored using UHPLC/MS analysis as it may undergo changes in concentration or chemical modification during survival assays. Figure 2 shows the evolution of oleacein concentration for up to 70 days in the S-base medium at a constant temperature of 20 °C. Stability was tested at 5 µg/mL and 20 µg/mL under the conditions as described above, and Figure 2 shows that oleacein was stable at both concentrations for 35 days, which is the maximal lifespan of most (N2) wild-type C. elegans.

3.2. Oleacein Effect on the Lifespan of (N2) Wild-Type C. elegans

To determine whether oleacein increases the longevity of C. elegans, an N2 wild-type strain of C. elegans adult nematodes was treated with increasing concentrations of oleacein (Figure 3, Table 1). Both S-base and DMSO controls correspond to, respectively, the medium conventionally used for maintaining nematode populations in liquid medium, and to the S-base medium supplemented with DMSO (cf. Section 2). As shown in Figure 3 and Table 1, mean lifespans were not significantly different between the two controls (LogRank p = 0.520), confirming that DMSO in the S-base does not have a significant impact on C. elegans.
Treatment of the nematodes with the lowest oleacein concentration (5 µg/mL) increased longevity by up to 24%—mean life expectancy of 19.1 ± 0.4 days compared to S-base and DMSO control media with a mean life expectancy of 15.8 ± 0.4 and 15.4 ± 0.4 days, respectively; LogRank p < 0.0001 in both cases. Increasing oleacein concentrations to 10 or 15 µg/mL reduced the positive effect, and when exposed to even greater concentrations of oleacein, further significant reductions in longevity were observed compared to both S-base and DMSO control groups (Table 1). At 20 µg/mL, the mean lifespan was 11.5 ± 0.4 days and at 30 µg/mL it was 8.5 ± 0.2 days with LogRank p < 0.0001 in both cases. These findings indicate that oleacein has a hormetic-like dose-dependent effect on the longevity of C. elegans.

3.3. Oleacein Is More Effective Than Hydroxytyrosol in Extending the Longevity of (N2) Wild-Type C. elegans

In a previous report, Brunetti et al. showed that hydroxytyrosol increases C. elegans longevity but at a considerably higher concentration (250 µg/mL) [38]. However, in this study, hydroxytyrosol at 5 µg/mL was compared to oleacein at the same concentration. As shown in Figure 4 and Table 2, as before, treatment with 5 µg/mL oleacein significantly increased the mean lifespan; however, the increase in lifespan with 5 µg/mL hydroxytyrosol was non-significant.

3.4. The Effect of Oleacein on the C. elegans Daf-16 Mutant

As shown above (Figure 3), oleacein at higher concentrations has a converse effect by reducing worm lifespan expectancy in comparison to controls. Because of the involvement of the C. elegans Daf-16 gene in hormesis and in longevity and stress resistance, particularly when boosted by phenolic compounds [56], the next step was to explore whether oleacein is involved in the Daf-16-dependent hormesis mechanism. To this end, the impact of oleacein on the lifespan of a C. elegans mutant for the Daf-16 gene was investigated. As shown in Figure 5A and Table 3, treatment of nematodes with 5 µg/mL oleacein resulted in a lifespan comparable to both controls. Conversely, treatment with 20 µg/mL oleacein reduced the mean lifespan by 34% relative to control S-base and DMSO; this was an effect that was highly significant (LogRank p > 0.0001). These results suggest that the positive effect of oleacein on (N2) wild-type C. elegans is Daf-16-dependent.

3.5. Oleacein Effect on Nuclear Translocation of DAF-16 Transcription Factor

In C. elegans, the transcription factor encoded by the hormetic gene Daf-16 can be activated by various stress factors through its relocation to the nucleus from its position in the cytoplasm and activation of transcriptional targets. Therefore, the next step was to determine whether, in the absence of any stressor, oleacein could trigger translocation of the DAF-16 transcription factor from the cytoplasm to the nucleus. Such an effect may explain the positive effect of oleacein observed on C. elegans lifespan at low concentrations. Therefore, a DAF-16::GFP transgenic strain that allows direct observation by fluorescence was used (see Section 2). As shown in Figure 6, treatment with 5 µg/mL oleacein increased the nuclear translocation of DAF-16 by 10%, and reduced cytoplasmic localization by 15% compared to the DMSO control.

3.6. Oleacein Effect on C. elegans Daf-2 Mutant

To further understand the ability of oleacein to activate DAF-16, the impact of oleacein on the lifespan of the C. elegans Daf-2 mutant was studied using the protocols described previously. As shown in Figure 5B, and summarized in Table 3, exposing Daf-2 mutant nematodes to 5 µg/mL oleacein significantly increased the mean lifespan by 21% compared to S-base and DMSO controls. Treatment with 20 µg/mL oleacein resulted in a lifespan comparable to controls. These results suggest that the positive effect of oleacein on wild-type (N2) C. elegans is independent of Daf-2, whereas the toxic effect could be countered by Daf-2 downregulation. The DAF-16 transcription factor, which reduces oxidative stress, is constitutively active in Daf-2 mutants. It may be supposed that oleacein toxicity at 20 µg/mL in the wild-type strain is related to an increase in oxidative stress.

3.7. Oleacein Effect on C. elegans Sir-2.1 Mutant

Because the positive effect of oleacein on (N2) wild-type C. elegans is independent of Daf-2, and its negative effect may be related to increased oxidative stress, the next step was to study the possibility of oleacein DAF-16 activation being related to the deacetylase SIR-2.1 protein using a Sir-2.1 mutant. As shown in Figure 5C and Table 3, 5 µg/mL oleacein resulted in a lifespan comparable to that of controls. This suggests that the positive effect of oleacein on (N2) wild-type C. elegans is SIR-2.1-dependent. Conversely, 20 µg/mL oleacein reduced the mean lifespan by almost 60% compared to controls; this was a difference that was highly significant—LogRank p > 0.0001. This negative effect seems to be greater on Sir-2.1 mutants compared to the wild-type strain, and may be due to the poor resistance of Sir-2.1 to oxidative stress, confirming that oleacein increases oxidative stress at higher doses.

3.8. Oleacein Effect on C. elegans Resistance to Thermal and Oxidative Stress

Stress resistance is known to be strongly linked to C. elegans longevity [57]. To better understand this effect, the ability of oleacein to increase C. elegans resistance to thermal and oxidative stress was investigated. As shown in Figure 7A, 5 µg/mL oleacein increased the survival of wild-type nematodes by almost 20%, with a 63.7% survival rate after 5 h of exposure at 35 °C, compared to a 44.6% survival rate for the DMSO control. Moreover, as shown in Figure 7B, treatment with 5 µg/mL oleacein increased wild-type survival by 15% after 30 min of exposure to H2O2—95.6% survival as compared to 80.3% survival for the DMSO control.

3.9. Biological Pathway Involved

In this study, oleacein had a hormetic-like dose-dependent effect on C. elegans longevity, with an increased lifespan at 5 µg/mL, no effect at 10 µg/mL and 15 µg/mL, and a reduced lifespan at 20 µg/mL and 30 µg/mL. Results showed that the low-dose positive effect of oleacein involved activation of the deacetylase SIR-2.1 protein, with subsequent activation of the transcription factor DAF-16. The negative effect of oleacein at 20 µg/mL or greater is probably related to increased oxidative stress. Based on these results, two mechanisms of action (Figure 8) may be proposed.
One mechanism is that oleacein is a true hormetic compound and is a source of oxidative stress in vivo. As stated previously, hormesis is characterized by a treatment that induces a beneficial effect at low doses and a deleterious effect at high doses. At low doses of oleacein (5 µg/mL), oxidative stress triggers the activation of SIR-2.1 and DAF-16, which allows transcription of antioxidant proteins with an overall positive effect on longevity. At the medium doses of 10 and 15 µg/mL, oxidative stress induced by oleacein is compensated for by the nematodes’ defense mechanisms, resulting in an overall zero effect. The higher concentration of 20 µg/mL has a negative impact on longevity when the effect of SIR-2.1/DAF-16 is overcompensated by the oxidative stress induced by oleacein.
The second possibility is that oleacein is not a true hormetic compound and only has a hormetic-like dose-dependent effect on survival. In this scenario, oleacein is a direct activator of SIR-2.1/DAF-16, increasing survival rates of C. elegans at the lower concentration. The negative effect of oleacein at the higher concentration of 20 µg/mL acts in a parallel pathway of unknown origin.

4. Discussion

The question of the hormetic nature of compounds has already been addressed for other phenolic compounds displaying the same dose–response effect, for example, quercetin or caffeic acid [58]. Many phenolic compounds were shown to increase C. elegans mean lifespan by 10 to 20% at concentrations of 18 to 250 µg/mL [58,59,60,61]. Other olive phenolics have shown similar activities, such as tyrosol which increased the mean lifespan by 21% at 35 µg/mL, or hydroxytyrosol which increased the mean lifespan by 14% at 250 µg/mL [38,62]. In a recent study, Cheng et al. showed that apigenin and chrysin could enhance C. elegans mean lifespan by, respectively, 23% at 10.8 µg/mL and 25% at 10.2 µg/mL [63]. It should be noted that in this study, oleacein at the lowest concentration of 5 µg/mL had a greater or similar impact on increasing lifespan than was previously reported for other phenolic compounds. Only Myricetin increased C. elegans lifespan to a significantly greater degree than oleacein (+33%), though at the considerably higher concentration of 160 µg/mL [64].
Together, these results—the first to identify the biological targets of oleacein—demonstrate the capacity of oleacein to increase lifespan and promote stress resistance in a C. elegans model, thereby contributing to the understanding of the beneficial effects of olive phenolics on health, in particular on healthy aging. Further experiments are necessary to explore the different mechanisms involved, especially regarding oxidative stress, though the findings of this study suggest oleacein is a true hormetic compound. Further studies on other in vivo models such as mice are needed to confirm this oleacein activity. Such explorations would contribute to a greater understanding of the action mechanisms involved in the activities of olive phenolic compounds and open avenues to their more effective and targeted exploitation in the future.

Author Contributions

Conceptualization, M.C., M.R., S.G. and D.M.-J.; methodology, M.C., M.R. and S.G.; software, M.C. and M.R.; validation, M.R., S.G. and D.M.-J.; formal analysis, M.C., M.R. and S.G.; investigation, M.C. and M.R.; resources, M.R., S.G. and D.M.-J.; data curation, M.C., M.R. and S.G.; writing—original draft preparation, M.C.; writing—review and editing, M.C., M.R., P.C., S.G. and D.M.-J.; visualization, M.C., M.R. and S.G.; supervision, M.R., S.G. and D.M.-J.; project administration, D.M.-J.; funding acquisition, D.M.-J. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the SATT-AxLR (Montpellier—France).

Institutional Review Board Statement

Ethical review and approval were waived for this study due to use of an invertebrate model.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.

Acknowledgments

We thank Mary Kelly, University of Montpellier, for kind language correction. Nematode strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Parkinson, L.; Cicerale, S. The Health Benefiting Mechanisms of Virgin Olive Oil Phenolic Compounds. Molecules 2016, 21, 1734. [Google Scholar] [CrossRef] [PubMed]
  2. Celano, R.; Piccinelli, A.L.; Pugliese, A.; Carabetta, S.; di Sanzo, R.; Rastrelli, L.; Russo, M. Insights into the Analysis of Phenolic Secoiridoids in Extra Virgin Olive Oil. J. Agric. Food Chem. 2018, 66, 6053–6063. [Google Scholar] [CrossRef] [PubMed]
  3. Bendini, A.; Cerretani, L.; Carrasco-Pancorbo, A.; Gómez-Caravaca, A.M.; Segura-Carretero, A.; Fernández-Gutiérrez, A.; Lercker, G. Phenolic Molecules in Virgin Olive Oils: A Survey of Their Sensory Properties, Health Effects, Antioxidant Activity and Analytical Methods. An Overview of the Last Decade. Molecules 2007, 12, 1679–1719. [Google Scholar] [CrossRef] [PubMed]
  4. Visioli, F.; Wolfram, R.; Richard, D.; Abdullah, M.I.C.B.; Crea, R. Olive Phenolics Increase Glutathione Levels in Healthy Volunteers. J. Agric. Food Chem. 2009, 57, 1793–1796. [Google Scholar] [CrossRef] [PubMed]
  5. Zhu, L.; Liu, Z.; Feng, Z.; Hao, J.; Shen, W.; Li, X.; Sun, L.; Sharman, E.; Wang, Y.; Wertz, K.; et al. Hydroxytyrosol Protects against Oxidative Damage by Simultaneous Activation of Mitochondrial Biogenesis and Phase II Detoxifying Enzyme Systems in Retinal Pigment Epithelial Cells. J. Nutr. Biochem. 2010, 21, 1089–1098. [Google Scholar] [CrossRef] [PubMed]
  6. Muriana, F.J.G.; la Paz, S.M.; Lucas, R.; Bermudez, B.; Jaramillo, S.; Morales, J.C.; Abia, R.; Lopez, S. Tyrosol and Its Metabolites as Antioxidative and Anti-Inflammatory Molecules in Human Endothelial Cells. Food Funct. 2017, 8, 2905–2914. [Google Scholar] [CrossRef] [PubMed]
  7. Wang, W.; Xia, Y.; Yang, B.; Su, X.; Chen, J.; Li, W.; Jiang, T. Protective Effects of Tyrosol against LPS-Induced Acute Lung Injury via Inhibiting NF-κB and AP-1 Activation and Activating the HO-1/Nrf2 Pathways. Biol. Pharm. Bull. 2017, 40, 583–593. [Google Scholar] [CrossRef]
  8. Aparicio-Soto, M.; Sánchez-Hidalgo, M.; Cárdeno, A.; González-Benjumea, A.; Fernández-Bolaños, J.G.; Alarcón-de-la-Lastra, C. Dietary Hydroxytyrosol and Hydroxytyrosyl Acetate Supplementation Prevent Pristane-Induced Systemic Lupus Erythematous in Mice. J. Funct. Foods 2017, 29, 84–92. [Google Scholar] [CrossRef]
  9. Gutierrez, M.B.; Magiatis, P.; Nieto, C.M.L. Use of Secoiridoids for the Treatment of Optic Neuritis. WO2020136221 A1, 2 July 2020. [Google Scholar]
  10. Vougogiannopoulou, K.; Lemus, C.; Halabalaki, M.; Pergola, C.; Werz, O.; Smith, A.B.; Michel, S.; Skaltsounis, L.; Deguin, B. One-Step Semisynthesis of Oleacein and the Determination as a 5-Lipoxygenase Inhibitor. J. Nat. Prod. 2014, 77, 441–445. [Google Scholar] [CrossRef]
  11. Xia, M.; Zhong, Y.; Peng, Y.; Qian, C. Olive Oil Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. Front. Nutr. 2022, 9, 1041203. [Google Scholar] [CrossRef]
  12. Martínez-González, M.A.; Sayón-Orea, C.; Bullón-Vela, V.; Bes-Rastrollo, M.; Rodríguez-Artalejo, F.; Yusta-Boyo, M.J.; García-Solano, M. Effect of Olive Oil Consumption on Cardiovascular Disease, Cancer, Type 2 Diabetes, and All-Cause Mortality: A Systematic Review and Meta-Analysis. Clin. Nutr. 2022, 41, 2659–2682. [Google Scholar] [CrossRef] [PubMed]
  13. Boronat, A.; Serreli, G.; Rodríguez-Morató, J.; Deiana, M.; de la Torre, R. Olive Oil Phenolic Compounds’ Activity against Age-Associated Cognitive Decline: Clinical and Experimental Evidence. Antioxidants 2023, 12, 1472. [Google Scholar] [CrossRef] [PubMed]
  14. Jiménez-Sánchez, A.; Martínez-Ortega, A.J.; Remón-Ruiz, P.J.; Piñar-Gutiérrez, A.; Pereira-Cunill, J.L.; García-Luna, P.P. Therapeutic Properties and Use of Extra Virgin Olive Oil in Clinical Nutrition: A Narrative Review and Literature Update. Nutrients 2022, 14, 1440. [Google Scholar] [CrossRef] [PubMed]
  15. Foscolou, A.; Critselis, E.; Tyrovolas, S.; Chrysohoou, C.; Sidossis, L.S.; Naumovski, N.; Matalas, A.-L.; Rallidis, L.; Polychronopoulos, E.; Ayuso-Mateos, J.L.; et al. The Effect of Exclusive Olive Oil Consumption on Successful Aging: A Combined Analysis of the ATTICA and MEDIS Epidemiological Studies. Foods 2019, 8, 25. [Google Scholar] [CrossRef] [PubMed]
  16. Fernández del Río, L.; Gutiérrez-Casado, E.; Varela-López, A.; Villalba, J.M. Olive Oil and the Hallmarks of Aging. Molecules 2016, 21, 163. [Google Scholar] [CrossRef]
  17. Riolo, R.; De Rosa, R.; Simonetta, I.; Tuttolomondo, A. Olive Oil in the Mediterranean Diet and Its Biochemical and Molecular Effects on Cardiovascular Health through an Analysis of Genetics and Epigenetics. Int. J. Mol. Sci. 2022, 23, 16002. [Google Scholar] [CrossRef] [PubMed]
  18. Roig, A.; Cayuela, M.L.; Sánchez-Monedero, M.A. An Overview on Olive Mill Wastes and Their Valorisation Methods. Waste Manag. 2006, 26, 960–969. [Google Scholar] [CrossRef] [PubMed]
  19. Kitsati, N.; Mantzaris, M.D.; Galaris, D. Hydroxytyrosol Inhibits Hydrogen Peroxide-Induced Apoptotic Signaling via Labile Iron Chelation. Redox Biol. 2016, 10, 233–242. [Google Scholar] [CrossRef] [PubMed]
  20. Mohan, V.; Das, S.; Rao, S.B.S. Hydroxytyrosol, a Dietary Phenolic Compound Forestalls the Toxic Effects of Methylmercury-Induced Toxicity in IMR-32 Human Neuroblastoma Cells. Environ. Toxicol. 2016, 31, 1264–1275. [Google Scholar] [CrossRef]
  21. Özbek, N.; Bali, E.; Karasu, C. Quercetin and Hydroxytyrosol Attenuates Xanthine/Xanthine Oxidase-Induced Toxicity in H9c2 Cardiomyocytes by Regulation of Oxidative Stress and Stress-Sensitive Signaling Pathways. Gen. Physiol. Biophys. 2015, 34, 407–414. [Google Scholar] [CrossRef]
  22. Nardi, M.; Bonacci, S.; De Luca, G.; Maiuolo, J.; Oliverio, M.; Sindona, G.; Procopio, A. Biomimetic Synthesis and Antioxidant Evaluation of 3,4-DHPEA-EDA [2-(3,4-Hydroxyphenyl) Ethyl (3S,4E)-4-Formyl-3-(2-Oxoethyl)Hex-4-Enoate]. Food Chem. 2014, 162, 89–93. [Google Scholar] [CrossRef] [PubMed]
  23. Paiva-Martins, F.; Fernandes, J.; Santos, V.; Silva, L.; Borges, F.; Rocha, S.; Belo, L.; Santos-Silva, A. Powerful Protective Role of 3,4-Dihydroxyphenylethanol−elenolic Acid Dialdehyde against Erythrocyte Oxidative-Induced Hemolysis. J. Agric. Food Chem. 2010, 58, 135–140. [Google Scholar] [CrossRef] [PubMed]
  24. Parzonko, A.; Czerwińska, M.E.; Kiss, A.K.; Naruszewicz, M. Oleuropein and Oleacein May Restore Biological Functions of Endothelial Progenitor Cells Impaired by Angiotensin II via Activation of Nrf2/Heme Oxygenase-1 Pathway. Phytomedicine 2013, 20, 1088–1094. [Google Scholar] [CrossRef] [PubMed]
  25. Morelló, J.-R.; Vuorela, S.; Romero, M.-P.; Motilva, M.-J.; Heinonen, M. Antioxidant Activity of Olive Pulp and Olive Oil Phenolic Compounds of the Arbequina Cultivar. J. Agric. Food Chem. 2005, 53, 2002–2008. [Google Scholar] [CrossRef] [PubMed]
  26. Gutiérrez-Miranda, B.; Gallardo, I.; Melliou, E.; Cabero, I.; Álvarez, Y.; Magiatis, P.; Hernández, M.; Nieto, M.L. Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects. Antioxidants 2020, 9, 1161. [Google Scholar] [CrossRef] [PubMed]
  27. Nikou, T.; Liaki, V.; Stathopoulos, P.; Sklirou, A.D.; Tsakiri, E.N.; Jakschitz, T.; Bonn, G.; Trougakos, I.P.; Halabalaki, M.; Skaltsounis, L.A. Comparison Survey of EVOO Polyphenols and Exploration of Healthy Aging-Promoting Properties of Oleocanthal and Oleacein. Food Chem. Toxicol. 2019, 125, 403–412. [Google Scholar] [CrossRef]
  28. Kenyon, C.J. The Genetics of Ageing. Nature 2010, 464, 504–512. [Google Scholar] [CrossRef] [PubMed]
  29. Château, M.-T.; Araiz, C.; Descamps, S.; Galas, S. Klotho Interferes with a Novel FGF-Signalling Pathway and Insulin/Igf-like Signalling to Improve Longevity and Stress Resistance in Caenorhabditis elegans. Aging 2010, 2, 567–581. [Google Scholar] [CrossRef]
  30. Stanfel, M.N.; Shamieh, L.S.; Kaeberlein, M.; Kennedy, B.K. The TOR Pathway Comes of Age. Biochim. Biophys. Acta 2009, 1790, 1067–1074. [Google Scholar] [CrossRef]
  31. Imai, S.; Guarente, L. NAD+ and Sirtuins in Aging and Disease. Trends Cell Biol. 2014, 24, 464–471. [Google Scholar] [CrossRef]
  32. Johnson, T.E. Advantages and Disadvantages of Caenorhabditis elegans for Aging Research. Exp. Gerontol. 2003, 38, 1329–1332. [Google Scholar] [CrossRef] [PubMed]
  33. Artal-Sanz, M.; de Jong, L.; Tavernarakis, N. Caenorhabditis elegans: A Versatile Platform for Drug Discovery. Biotechnol. J. 2006, 1, 1405–1418. [Google Scholar] [CrossRef] [PubMed]
  34. Weinkove, D.; Zavagno, G. Applying C. elegans to the Industrial Drug Discovery Process to Slow Aging. Front. Aging 2021, 2, 740582. [Google Scholar] [CrossRef] [PubMed]
  35. Papaevgeniou, N.; Chondrogianni, N. Anti-Aging and Anti-Aggregation Properties of Polyphenolic Compounds in C. elegans. Curr. Pharm. Des. 2018, 24, 2107–2120. [Google Scholar] [CrossRef] [PubMed]
  36. Saul, N.; Pietsch, K.; Stürzenbaum, S.R.; Menzel, R.; Steinberg, C.E.W. Diversity of Polyphenol Action in Caenorhabditis elegans: Between Toxicity and Longevity. J. Nat. Prod. 2011, 74, 1713–1720. [Google Scholar] [CrossRef] [PubMed]
  37. Wilson, M.A.; Shukitt-Hale, B.; Kalt, W.; Ingram, D.K.; Joseph, J.A.; Wolkow, C.A. Blueberry Polyphenols Increase Lifespan and Thermotolerance in Caenorhabditis elegans. Aging Cell 2006, 5, 59–68. [Google Scholar] [CrossRef]
  38. Brunetti, G.; Di Rosa, G.; Scuto, M.; Leri, M.; Stefani, M.; Schmitz-Linneweber, C.; Calabrese, V.; Saul, N. Healthspan Maintenance and Prevention of Parkinson’s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans. Int. J. Mol. Sci. 2020, 21, 2588. [Google Scholar] [CrossRef] [PubMed]
  39. Gems, D.; Partridge, L. Stress-Response Hormesis and Aging: “That Which Does Not Kill Us Makes Us Stronger”. Cell Metab. 2008, 7, 200–203. [Google Scholar] [CrossRef] [PubMed]
  40. Le Bourg, E.; Rattan, S. Mild Stress and Healthy Aging: Applying Hormesis in Aging Research and Interventions; Springer: Berlin/Heidelberg, Germany, 2008; p. 187. [Google Scholar]
  41. Rattan, S.I.S. Hormetins as Novel Components of Cosmeceuticals and Aging Interventions. Cosmetics 2015, 2, 11–20. [Google Scholar] [CrossRef]
  42. Le Bourg, E.; Rattan, S. (Eds.) Hormesis in Health and Disease; CRC Press: Boca Raton, FL, USA, 2014; ISBN 978-0-429-17107-9. [Google Scholar]
  43. Mattson, M.P. Hormesis Defined. Ageing Res. Rev. 2008, 7, 1–7. [Google Scholar] [CrossRef]
  44. Calabrese, E.J. Converging Concepts: Adaptive Response, Preconditioning, and the Yerkes–Dodson Law Are Manifestations of Hormesis. Ageing Res. Rev. 2008, 7, 8–20. [Google Scholar] [CrossRef] [PubMed]
  45. Cypser, J.R.; Tedesco, P.; Johnson, T.E. Hormesis and Aging in Caenorhabditis elegans. Exp. Gerontol. 2006, 41, 935–939. [Google Scholar] [CrossRef] [PubMed]
  46. Cypser, J.R.; Johnson, T.E. Hormesis in Caenorhabditis elegans Dauer-Defective Mutants. Biogerontology 2003, 4, 203–214. [Google Scholar] [CrossRef] [PubMed]
  47. Hartwig, K.; Heidler, T.; Moch, J.; Daniel, H.; Wenzel, U. Feeding a ROS-Generator to Caenorhabditis elegans Leads to Increased Expression of Small Heat Shock Protein HSP-16.2 and Hormesis. Genes Nutr. 2009, 4, 59–67. [Google Scholar] [CrossRef] [PubMed]
  48. Senchuk, M.M.; Dues, D.J.; Schaar, C.E.; Johnson, B.K.; Madaj, Z.B.; Bowman, M.J.; Winn, M.E.; Van Raamsdonk, J.M. Activation of DAF-16/FOXO by Reactive Oxygen Species Contributes to Longevity in Long-Lived Mitochondrial Mutants in Caenorhabditis elegans. PLoS Genet. 2018, 14, e1007268. [Google Scholar] [CrossRef] [PubMed]
  49. Kenyon, C.; Chang, J.; Gensch, E.; Rudner, A.; Tabtiang, R. A C. elegans Mutant That Lives Twice as Long as Wild Type. Nature 1993, 366, 461–464. [Google Scholar] [CrossRef] [PubMed]
  50. Mukhopadhyay, A.; Oh, S.W.; Tissenbaum, H.A. Worming Pathways to and from DAF-16/FOXO. Exp. Gerontol. 2006, 41, 928–934. [Google Scholar] [CrossRef] [PubMed]
  51. Viswanathan, M.; Kim, S.K.; Berdichevsky, A.; Guarente, L. A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span. Dev. Cell 2005, 9, 605–615. [Google Scholar] [CrossRef] [PubMed]
  52. Berdichevsky, A.; Viswanathan, M.; Horvitz, H.R.; Guarente, L. C. elegans SIR-2.1 Interacts with 14-3-3 Proteins to Activate DAF-16 and Extend Life Span. Cell 2006, 125, 1165–1177. [Google Scholar] [CrossRef]
  53. Wang, Y.; Tissenbaum, H.A. Overlapping and Distinct Functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech. Ageing Dev. 2006, 127, 48–56. [Google Scholar] [CrossRef]
  54. Stiernagle, T. Maintenance of C. elegans. In WormBook; The C. elegans Research Community, Ed.; WormBook Research Community: Pasadena, CA, USA, 2006. [Google Scholar]
  55. Brenner, S. The Genetics of Caenorhabditis elegans. Genetics 1974, 77, 71–94. [Google Scholar] [CrossRef] [PubMed]
  56. Liu, L.; Guo, P.; Wang, P.; Zheng, S.; Qu, Z.; Liu, N. The Review of Anti-Aging Mechanism of Polyphenols on Caenorhabditis elegans. Front. Bioeng. Biotechnol. 2021, 9, 635768. [Google Scholar] [CrossRef] [PubMed]
  57. Zhou, K.I.; Pincus, Z.; Slack, F.J. Longevity and Stress in Caenorhabditis elegans. Aging 2011, 3, 733–753. [Google Scholar] [CrossRef] [PubMed]
  58. Pietsch, K.; Saul, N.; Chakrabarti, S.; Stürzenbaum, S.R.; Menzel, R.; Steinberg, C.E.W. Hormetins, Antioxidants and Prooxidants: Defining Quercetin, Caffeic Acid and Rosmarinic Acid-Mediated Life Extension in C. elegans. Biogerontology 2011, 12, 329–347. [Google Scholar] [CrossRef] [PubMed]
  59. Saul, N.; Pietsch, K.; Menzel, R.; Stürzenbaum, S.R.; Steinberg, C.E.W. The Longevity Effect of Tannic Acid in Caenorhabditis elegans: Disposable Soma Meets Hormesis. J. Gerontol. 2010, 65A, 626–635. [Google Scholar] [CrossRef] [PubMed]
  60. Schlernitzauer, A.; Oiry, C.; Hamad, R.; Galas, S.; Cortade, F.; Chabi, B.; Casas, F.; Pessemesse, L.; Fouret, G.; Feillet-Coudray, C.; et al. Chicoric Acid Is an Antioxidant Molecule That Stimulates AMP Kinase Pathway in L6 Myotubes and Extends Lifespan in Caenorhabditis elegans. PLoS ONE 2013, 8, e78788. [Google Scholar] [CrossRef] [PubMed]
  61. Zheng, S.-Q.; Huang, X.-B.; Xing, T.-K.; Ding, A.-J.; Wu, G.-S.; Luo, H.-R. Chlorogenic Acid Extends the Lifespan of Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway. J. Gerontol. A Biol. Sci. Med. Sci. 2017, 72, 464–472. [Google Scholar] [CrossRef] [PubMed]
  62. Cañuelo, A.; Gilbert-López, B.; Pacheco-Liñán, P.; Martínez-Lara, E.; Siles, E.; Miranda-Vizuete, A. Tyrosol, a Main Phenol Present in Extra Virgin Olive Oil, Increases Lifespan and Stress Resistance in Caenorhabditis elegans. Mech. Ageing Dev. 2012, 133, 563–574. [Google Scholar] [CrossRef] [PubMed]
  63. Cheng, Y.; Hou, B.-H.; Xie, G.-L.; Shao, Y.-T.; Yang, J.; Xu, C. Transient Inhibition of Mitochondrial Function by Chrysin and Apigenin Prolong Longevity via Mitohormesis in C. elegans. Free Radic. Biol. Med. 2023, 203, 24–33. [Google Scholar] [CrossRef]
  64. Büchter, C.; Ackermann, D.; Havermann, S.; Honnen, S.; Chovolou, Y.; Fritz, G.; Kampkötter, A.; Wätjen, W. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16. Int. J. Mol. Sci. 2013, 14, 11895–11914. [Google Scholar] [CrossRef]
Foods 13 02146 g001
Figure 1. Oleacein structure.
Figure 1. Oleacein structure.
Foods 13 02146 g001
Foods 13 02146 g002
Figure 2. Oleacein stability in S-base at 20 °C.
Figure 2. Oleacein stability in S-base at 20 °C.
Foods 13 02146 g002
Foods 13 02146 g003
Figure 3. Oleacein impact on wild-type (N2) C. elegans lifespan.
Figure 3. Oleacein impact on wild-type (N2) C. elegans lifespan.
Foods 13 02146 g003
Foods 13 02146 g004
Figure 4. Comparative effects of oleacein and hydroxytyrosol treatment on wild-type C. elegans lifespan.
Figure 4. Comparative effects of oleacein and hydroxytyrosol treatment on wild-type C. elegans lifespan.
Foods 13 02146 g004
Foods 13 02146 g005
Figure 5. Effect of oleacein on C. elegans mutants’ lifespan.
Figure 5. Effect of oleacein on C. elegans mutants’ lifespan.
Foods 13 02146 g005
Foods 13 02146 g006
Figure 6. Effect of oleacein on DAF-16::GFP cellular localization.
Figure 6. Effect of oleacein on DAF-16::GFP cellular localization.
Foods 13 02146 g006
Foods 13 02146 g007
Figure 7. Effect of oleacein on wild-type C. elegans thermal (A) and oxidative stress (B) resistance.
Figure 7. Effect of oleacein on wild-type C. elegans thermal (A) and oxidative stress (B) resistance.
Foods 13 02146 g007
Foods 13 02146 g008
Figure 8. Possible mechanisms of action of oleacein.
Figure 8. Possible mechanisms of action of oleacein.
Foods 13 02146 g008
Table 1. Oleacein-dependent lifespan modulation of wild-type C. elegans.
Table 1. Oleacein-dependent lifespan modulation of wild-type C. elegans.
Treatment50th Percentile (Days)Mean Lifespan (Days ± SD)Max Lifespan (Days)CodeStatistics
(KM Analysis)		N (Censored)
p = 0.520 (B)
p < 0.0001 (C)
Control S-base1515.8 ± 0.4 30Ap < 0.0001 (D)
p = 0.401 (E)
p = 0.375 (F)
p < 0.0001 (G)		153 (1)
p = 0.520 (A)
p < 0.0001 (C)
Control DMSO1415.4 ± 0.436Bp < 0.0001 (D)
p = 0.530 (E)
p = 0.256 (F)
p < 0.0001 (G)		151 (3)
p < 0.0001 (A)
p < 0.0001 (B)
30 µg/mL98.5 ± 0.215Cp < 0.0001 (D)
p < 0.0001 (E)
p < 0.0001 (F)
p < 0.0001 (G)		151 (0)
p < 0.0001 (A)
p < 0.0001 (B)
20 µg/mL1011.5 ± 0.429Dp < 0.0001 (C)
p < 0.0001 (E)
p < 0.0001 (F)
p < 0.0001 (G)		151 (0)
p = 0.401 (A)
p = 0.530 (B)
15 µg/mL1414.8 ± 0.535Ep < 0.0001 (C)
p < 0.0001 (D)
p = 0.102 (F)
p < 0.0001 (G)		154 (2)
p = 0.375 (A)
p = 0.256 (B)
10 µg/mL1515.9 ± 0.641Fp < 0.0001 (C)
p < 0.0001 (D)
p = 0.102 (E)
p = 0.007 (G)		153 (1)
p < 0.0001 (A)
p < 0.0001 (B)
5 µg/mL2019.1 ± 0.434Gp < 0.0001 (C)
p < 0.0001 (D)
p < 0.0001 (E)
p = 0.007 (F)		151 (3)
Table 2. Comparative effects of oleacein and hydroxytyrosol treatment on wild-type C. elegans lifespan.
Table 2. Comparative effects of oleacein and hydroxytyrosol treatment on wild-type C. elegans lifespan.
Treatment50th Percentile (Days)Mean Lifespan (Days ± SD)Max Lifespan (Days)CodeStatistics
(KM Analysis)		N (Censored)
25 p = 0.577 (B)
Control S-base1313.5 ± 0.3 Ap < 0.0001 (C)158 (2)
p = 0.504 (D)
25 p = 0.577 (A)
Control DMSO1313.7 ± 0.3Bp < 0.0001 (C)155 (4)
p = 0.238 (D)
41 p < 0.0001 (A)
Oleacein 5 µg/mL1616.7 ± 0.4Cp < 0.0001 (B)160 (4)
p < 0.0001 (D)
23 p = 0.504 (A)
Hydroxytyrosol 5 µg/mL1313.3 ± 0.3Dp = 0.238 (B)154 (1)
p < 0.0001 (C)
Table 3. Effect of oleacein on C. elegans mutants’ lifespan.
Table 3. Effect of oleacein on C. elegans mutants’ lifespan.
StrainTreatment50th Percentile (Days)Mean Lifespan (Days ± SD)Max Lifespan (Days)CodeStatistics (KM Analysis)N (Censored)
28 p = 0.711 (B)
Daf-16 (mgDf50)Control S-base1412.9 ± 0.4Ap < 0.0001 (C)153 (3)
p = 0.128 (D)
28 p = 0.711 (A)
Daf-16 (mgDf50)Control DMSO1413.1 ± 0.4Bp < 0.0001 (C)151 (1)
p = 0.291 (D)
20 p < 0.0001 (A)
Daf-16 (mgDf50)20 µg/mL88.60 ± 0.28Cp < 0.0001 (B)152 (1)
p < 0.0001 (D)
28 p = 0.128 (A)
Daf-16 (mgDf50)5 µg/mL1514.1 ± 0.4Dp = 0.291 (B)153 (1)
p < 0.0001 (C)
74 p = 0.250 (B)
Daf-2 (e1370)Control S-base3233.8 ± 1.3Ap = 0.916 (C)148 (2)
p = 0.0003 (D)
65 p = 0.250 (A)
Daf-2 (e1370)Control DMSO3231.8 ± 1.2Bp = 0.382 (C)152 (6)
p < 0.0001 (D)
p = 0.916 (A)
Daf-2 (e1370)20 µg/mL3233.9 ± 1.276Cp = 0.382 (B)154 (2)
p = 0.0003 (D)
76 p = 0.0003 (A)
Daf-2 (e1370)5 µg/mL4339.6 ± 1.6Dp < 0.0001 (B)155 (11)
p = 0.0003 (C)
31 p = 0.544 (B)
Sir-2.1 (ok434)Control S-base1715.7 ± 0.4Ap < 0.0001 (C)153 (2)
p = 0.811 (D)
31 p = 0.544 (A)
Sir-2.1 (ok434)Control DMSO1415.3 ± 0.4Bp < 0.0001 (C)149 (4)
p = 0.454 (D)
18 p < 0.0001 (A)
Sir-2.1 (ok434)20 µg/mL77.39 ± 0.30Cp < 0.0001 (B)151 (1)
p < 0.0001 (D)
35 p = 0.811 (A)
Sir-2.1 (ok434)5 µg/mL1715.3 ± 0.5Dp = 0.454 (B)149 (5)
p < 0.0001 (C)
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Carrara, M.; Richaud, M.; Cuq, P.; Galas, S.; Margout-Jantac, D. Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance. Foods 2024, 13, 2146. https://doi.org/10.3390/foods13132146

AMA Style

Carrara M, Richaud M, Cuq P, Galas S, Margout-Jantac D. Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance. Foods. 2024; 13(13):2146. https://doi.org/10.3390/foods13132146

Chicago/Turabian Style

Carrara, Morgane, Myriam Richaud, Pierre Cuq, Simon Galas, and Delphine Margout-Jantac. 2024. "Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance" Foods 13, no. 13: 2146. https://doi.org/10.3390/foods13132146

APA Style

Carrara, M., Richaud, M., Cuq, P., Galas, S., & Margout-Jantac, D. (2024). Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance. Foods, 13(13), 2146. https://doi.org/10.3390/foods13132146

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop