Elsevier

Experimental Gerontology

Volume 144, February 2021, 111190
Experimental Gerontology

Purple Sweet Potato Extract extends lifespan by activating autophagy pathway in male Drosophila melanogaster

https://doi.org/10.1016/j.exger.2020.111190Get rights and content

Abstract

Introduction

Purple sweet potato is a nutritive food rich in anthocyanins that possess antioxidant effects. Drosophila melanogaster owns short growth cycle, fast reproduction, less chromosomes, more mutants, small individuals, therefore, which is an appropriate genetic model organism.

Objective

To investigate the anti-aging activity of Purple Sweet Potato Extract (PSPE) in male Drosophila melanogaster and explore the underlying mechanism.

Results

PSPE-induced longevity was associated with improvements in climbing ability and tolerance to stressors such as paraquat and hydrogen peroxide (H2O2). Furthermore, PSPE supplementation increased the activity of superoxide dismutase (SOD) and catalase (CAT), as well as expression of SOD and CAT genes, but decreased malondialdehyde (MDA) content. Meanwhile, PSPE decreased the intestinal stem cells (ISCs) proliferation and improved intestinal homeostasis, which was measured by Smurf assay and colony-forming units (CFUs) measurement in aging flies. Additionally, PSPE markedly inhibited the expression of upstream genes AKT-1, PI3K and mTOR and elevated the downstream gene 4E-BP, which further activated the expression of autophagy-related genes (Atg1, Atg5, Atg8a and Atg8b). Moreover, the production of lysosomes increased, indicating that the autophagy pathway was activated.

Conclusion

The results provided direct evidence of PSPE anti-aging effects on an organism level, indicating PSPE could be developed for use in effective anti-aging products.

Introduction

Aging impacts various bodily functions, such as stress tolerance and homeostasis; however, its effects can be mitigated via the autophagy signaling pathway to prolong an organism's lifespan (Liu et al., 2020). Intestinal barrier defects could shorten an organism's lifespan, therefore, intestinal barrier dysfunction is a good marker of aging (Rera et al., 2013). In recent studies, maintenance of intestinal homeostasis in Drosophila melanogaster has been a hot topic (Woodcock et al., 2015). Many efforts have been made to develop strategies that delay senescence by preserving intestinal homeostasis.

Purple sweet potato (Ipomoea batatas L) is a member of the sweet potato family, it is a kind of natural functional food with high edible and medicinal value (Kano et al., 2014). In recent years, purple sweet potato has received enormous attention due to its cheap source, role in health care and range of colors. It contains plentiful anthocyanins which have been reported to show high pH stability, thermostability and antioxidant activity (Chen et al., 2019). Moreover, purple sweet potato anthocyanins are more stable than other plants such as blueberries, cranberries and strawberries, therefore, the purple sweet potato has been suggested as a good source of stable anthocyanins (Hwang et al., 2011). In recent study, purple sweet potato anthocyanins ameliorated oxidative Stress, inflammation among chronic constriction injury-induced neuropathic pain in rats (Widyadharma et al., 2020). Therefore, PSPE may be an potential functional food to delay aging.

Drosophila melanogaster was an ideal model for short life cycle, rapid reproduction and low cost, moreover, it was used as a research model due to its strong genetics, conserved disease pathways and 75% pathogenic genes of flies are homologous to humans (Brown et al., 2014). As female flies produced more female hormone which effected lifespan in flies, while the hormone of male flies was at a low level, thus, we used male flies as model organism in the study (Li et al., 2019).

The mammalian Target of Rapamycin (mTOR) signaling pathway regulates organismal growth and homeostasis by sensing changes in the environment. It is involved in many human ailments, including diabetes and Alzheimer's Disease premature senility. A recent study found evidence suggesting that a physical association between mTOR and autophagy plays a key role in the activation of the mTOR pathway (Nazio et al., 2013). Recently, it was reported that purple sweet potato color improved cognitive deficits in high-fat-diet feeding mice by enhancing autophagy (Zhuang et al., 2019). However, it is still unclear whether PSPE extends the lifespan of flies by activating autophagy pathway.

To test the hypothesis, the present study used male Drosophila melanogaster to explore the mechanism of anti-aging effects of PSPE supplementation. The results showed that PSPE extended the lifespan, improved the climbing ability and stress tolerance, and dramatically improved intestinal homeostasis and integrity in flies. Moreover, PSPE increased the antioxidant enzyme activity and gene expressions, inhibited the mTOR pathway, and activated the autophagy pathway, thus, extending the lifespan in flies.

Section snippets

Materials and reagents

PSPE was purchased from Tianjin Jianfeng Natural Product R&D Co., Ltd., (Tianjin, China). The SOD, CAT and MDA assay kits used were the products of Nanjing Jiancheng Bioengineering Institute (Nanjing, China). TRIzol Reagent, High Capacity cDNA Reverse Transcription Kit, and SYBR Green Kit were purchased from Takara Biological Engineering Co., Ltd. (Takara). FD&C Blue No. 1 and LysoTracker Red were purchased from Sigma Chemical (St Louis, MO, USA). Analytical grade agar, glucose, alcohol,

Phytochemical profiles of extracts

The anthocyanins of PSPE were identified by LC-MS. The molecular ions and important fragment ions were compared with Zhao et al.'s report for identification (Zhao et al., 2014). In total, eight different compounds (including one unknown) were isolated and identified using UV and LC-ESI spectra. The basic structure of the anthocyanins isolated from PSPE was modified by structures that have been named in Fig. 1A. Eight peaks showed on the MS chromatogram of anthocyanins from PSPE (Fig. 1B). The

Discussion

Purple sweet potatoes are rich in anthocyanin and other phenolic compounds with known antioxidant activities (Ju et al., 2011). It is previously reported that purple sweet potato have various functions, for example, anti-aging, anti-inflammation, anti-atherosclerosis (Sun et al., 2015). Therefore, PSPE was a potential functional food to delay senescence. It is confirmed that the efficacy of functional food tend to vary with sex in flies, in addition, the hormone of male flies was at a low

Conclusions

PSPE extended the lifespan and increased climbing ability, decreased the mortality rates induced by paraquat and H2O2, improved intestinal homeostasis and intestinal barrier dysfunction, increased the activities of antioxidant enzymes and gene expression, inhibited mTOR and activated the autophagy pathway in flies. These results indicate PSPE is potential to be anti-aging products, and provide references for further anti-aging studies on human beings, and the improvement effect of PSPE

CRediT authorship contribution statement

In the manuscript, the red words which were signed have been modified.

Declaration of competing interest

The authors declare no competing financial interest.

Acknowledgements

We thank all authors for invaluable comments on the manuscript.

Funding

This work was fund by Tianjin science and technology project (17KPHDSF00120), the Natural Science Foundation of Tianjin (No. 18JCYBJC26500).

References (41)

  • K.J. Woodcock et al.

    Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in drosophila fed a lipid-rich diet

    Immunity

    (2015)
  • J.G. Zhao et al.

    Isolation and identification of colourless caffeoyl compounds in purple sweet potato by HPLC-DAD-ESI/MS and their antioxidant activities

    Food Chem.

    (2014)
  • J. Zhuang et al.

    Purple sweet potato color protects against high-fat diet-induced cognitive deficits through AMPK-mediated autophagy in mouse hippocampus

    J. Nutr. Biochem.

    (2019)
  • A. Bhukel et al.

    Spermidine boosts autophagy to protect from synapse aging

    Autophagy.

    (2016)
  • J.B. Brown et al.

    Diversity and dynamics of the Drosophila transcriptome

    Nature

    (2014)
  • N. Buchon et al.

    Gut homeostasis in a microbial world: insights from Drosophila melanogaster

    Nat Rev Microbiol

    (2013)
  • R.D. Cabo et al.

    The search for antiaging interventions: from elixirs to fasting regimens

    Cell

    (2014)
  • D. Chattopadhyay et al.

    Longevity-promoting efficacies of rutin in high fat diet fed Drosophila melanogaster

    Biogerontology

    (2020)
  • D.S. Evans et al.

    TOR signaling never gets old: aging, longevity and TORC1 activity

    Ageing Res. Rev.

    (2011)
  • X. Fan et al.

    Rapamycin preserves gut homeostasis during Drosophila aging

    Oncotarget

    (2015)
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