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Salidroside promotes healthy longevity by interfering with HSP90 activity

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Abstract

Aging is a risk factor for human health and quality of life. Screening and development of novel supplements and medications to combat aging and delay the incidence of age-related diseases are of great significance. In this study, salidroside (SA), a primary natural small molecule from Rhodiola rosea, was investigated regarding its effects on life and healthspan and the underlying molecular mechanism(s) of anti-aging and antioxidation. Our results showed that SA effectively prolonged lifespan and exhibited anti-aging and antioxidative properties. Computer-assisted methods, label-free interaction analysis, and in vitro assays showed that SA directly bound heat shock protein 90 (HSP90). Furthermore, SA significantly inhibited the ATPase activity of HSP90, affecting the interaction between HSP90 and its interacting proteins and the expression of downstream genes to regulate lifespan and the oxidative stress response. Our findings provided new insights into the pharmacological properties of SA across multiple species and its potential as an anti-aging drug.

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All data needed to evaluate the conclusions in the paper are present in the main text or the Supplementary Materials. Additional data related to this article may be requested from the authors.

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Funding

This project was supported by the National Natural Science Foundation of China (NSFC) to F. D. (No. 31830094) and to J. S. (No. 32272939), Fundamental Research Funds for the central Universities to L. Z. (SWU120011), National Natural Science Foundation of China to L. Z. (No. 32000810), and No. U20A2058 from NSFC to X. T. Additional support was provided by Funds of China Agriculture Research System of MOF and MARA CARS-18-ZJ0102 from the Ministry of Agriculture and Rural Affairs of the People’s Republic of China to F. D.

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Author notes

  1. Jianfei Zhang, Zhiquan Li and Jiangbo Song contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Resource Insects, Key Laboratory of Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Science, Southwest University, Chongqing, 400715, China

    Jianfei Zhang, Jiangbo Song, Lei Zhou, Xin Chen, Wen Ge, Tianyi Dong, Yuxin Luo, Ting Mao, Zheng Li, Duan Tan, Xiaoling Tong & Fangyin Dai

  2. Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark

    Zhiquan Li, Lene Juel Rasmussen & Vilhelm A. Bohr

  3. Section on DNA Repair, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Vilhelm A. Bohr

Authors
  1. Jianfei Zhang
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  2. Zhiquan Li
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Contributions

F. D. conceived the study. F. D., J. Z., Z. L., J. S., and X. T. designed the experimental plan. J. Z., L. Z., J. S., W. G., and Y. L. performed experiments. T. D. assisted silkworm rearing and feeding experiment. X. C., Z. L., D. T., and T. M. analyzed the data and prepared figures. F. D., J. Z., Z. L., J. S., V. B., and L. J. R. wrote the manuscript. All authors discussed the results at all stages of the manuscript preparation.

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Correspondence to Fangyin Dai.

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Zhang, J., Li, Z., Song, J. et al. Salidroside promotes healthy longevity by interfering with HSP90 activity. GeroScience 46, 1641–1655 (2024). https://doi.org/10.1007/s11357-023-00921-3

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