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Chronic exposure to rapamycin and episodic serum starvation modulate ageing of human fibroblasts in vitro

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Abstract

Mild stress-induced activation of stress response (SR) pathways, such as autophagy, heat shock response, oxidative SR, DNA damage response, and inflammatory response, can be potentially health beneficial. Using the model system of cellular ageing and replicative senescence in vitro, we have studied the ageing modulatory effects of the two conditions, rapamycin and serum starvation. Chronic exposure to 0.1, 1 and 10 nM rapamycin positively modulated the survival, growth, morphology, telomere length, DNA methylation levels, 8-oxo-dG level in DNA, N6-methyl-adenosine level in RNA, and ethanol stress tolerance of serially passaged normal human skin fibroblasts. Furthermore, episodic (once a week) serum starvation of human skin fibroblasts extended their replicative lifespan by about 22%, along with the maintenance of early passage youthful morphology even in late passage cultures. Although the results of this study may be considered preliminary, it can be inferred that intermittent and episodic induction of SR, rather than chronic up-regulation of SR, is more effective and applicable in the practice of hormesis for healthy ageing and longevity.

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Acknowledgements

We are thankful to the Laboratory Technician Bente Andersen for all her work on the serum deprivation series of experiments. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 633589. This publication reflects only the authors’ views and the Commission is not responsible for any use that may be made of the information it contains.

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Authors and Affiliations

  1. Laboratory of Cellular Ageing, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

    Lakshman Sodagam & Suresh I. S. Rattan

  2. Laboratory of Cell Biology, University of Rzeszow, Rzeszow, Poland

    Anna Lewinska

  3. Department of Genetics, University of Rzeszow, Rzeszow, Poland

    Maciej Wnuk

Authors
  1. Lakshman Sodagam
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  2. Anna Lewinska
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  3. Maciej Wnuk
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  4. Suresh I. S. Rattan
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Correspondence to Suresh I. S. Rattan.

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Sodagam, L., Lewinska, A., Wnuk, M. et al. Chronic exposure to rapamycin and episodic serum starvation modulate ageing of human fibroblasts in vitro. Biogerontology 18, 841–854 (2017). https://doi.org/10.1007/s10522-017-9730-8

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  • DOI: https://doi.org/10.1007/s10522-017-9730-8

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