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Dietary intake of diosgenin delays aging of male fish Nothobranchius guentheri through modulation of multiple pathways that play prominent roles in ROS production

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Abstract

Oxidative stress including DNA damage, increased lipid and protein oxidation, is an important feature of aging. Diosgenin (DG) has been shown to have diverse biological effects, including amelioration of aging-related cognition deficits, but the anti-aging activity of DG has not been tested before in animal models. In the present study, we clearly demonstrated that dietary intake of DG extended both mean and maximum lifespans of the male fish Nothobranchius guentheri by approximately 3.23 and 3.67 weeks, respectively, reduced the accumulation of lipofuscin (LF) in the gills and senescence-associated-β-galactosidase (SA-β-Gal) in the caudal fins, and lowered the levels of protein oxidation, lipid peroxidation and reactive oxygen species (ROS) in the muscles, indicating that DG possesses rejuvenation and anti-aging property. We also showed that DG enhanced the activity of antioxidant enzymes, including catalase, superoxide dismutase and glutathione peroxidase, promoted the proteolytic activity of the ubiquitin–proteasome pathway, and suppressed the phosphatidylinositol 3-kinase/protein kinase/molecular target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Altogether, this study highlights for the first time the rejuvenation and anti-aging property of the naturally occurring steroidal sapogenin DG. It also suggests that DG exerts its rejuvenation and anti-aging activity through modulation of multiple signaling pathways that play prominent roles in ROS production.

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Acknowledgements

We thank all the participants for their valuable contribution to this study.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 32073000) and the Ministry of Science and Technology (Grant No. 2018YFD0900505).

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Authors and Affiliations

  1. Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China

    Lili Song, Congjun Li, Fei Wu & Shicui Zhang

  2. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266003, China

    Shicui Zhang

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  1. Lili Song
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  2. Congjun Li
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  3. Fei Wu
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  4. Shicui Zhang
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Contributions

SZ and LS designed the experiments and wrote the paper; LS, CL and FW performed the experiments; LS and SZ analyzed the data; and all authors approved the final version of the manuscript.

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Correspondence to Shicui Zhang.

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Song, L., Li, C., Wu, F. et al. Dietary intake of diosgenin delays aging of male fish Nothobranchius guentheri through modulation of multiple pathways that play prominent roles in ROS production. Biogerontology 23, 201–213 (2022). https://doi.org/10.1007/s10522-022-09955-0

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