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Adding intrinsically disordered proteins to biological ageing clocks

Nature Cell Biology volume 26, pages 851–858 (2024)Cite this article

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Abstract

Research into how the young and old differ, and which biomarkers reflect the diverse biological processes underlying ageing, is a current and fast-growing field. Biological clocks provide a means to evaluate whether a molecule, cell, tissue or even an entire organism is old or young. Here we summarize established and emerging molecular clocks as timepieces. We emphasize that intrinsically disordered proteins (IDPs) tend to transform into a β-sheet-rich aggregated state and accumulate in non-dividing or slowly dividing cells as they age. We hypothesize that understanding these protein-based molecular ageing mechanisms might provide a conceptual pathway to determining a cell’s health age by probing the aggregation state of IDPs, which we term the IDP clock.

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Fig. 1: The IDP clock.
Fig. 2: Main challenges for reading the IDP clock in vivo.

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Acknowledgements

We thank all members of the Dormann and Lemke laboratories for discussions, and P. Baumann and C. Niehrs for discussions on the telomere and methylation clocks. We are grateful to N. Heinss for her creative work on illustrations. D.D. and E.A.L. acknowledge funding from the CRC1551 “Polymer concepts in cellular function” of the Deutsche Forschungsgemeinschaft (project number 464588647).

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  1. Biocenter, Johannes Gutenberg University, Mainz, Germany

    Dorothee Dormann & Edward Anton Lemke

  2. Institute for Molecular Biology, Mainz, Germany

    Dorothee Dormann & Edward Anton Lemke

  3. Institute for Quantitative and Computational Biosciences, Johannes Gutenberg University, Mainz, Germany

    Edward Anton Lemke

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  1. Dorothee Dormann
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  2. Edward Anton Lemke
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Correspondence to Dorothee Dormann or Edward Anton Lemke.

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Dormann, D., Lemke, E.A. Adding intrinsically disordered proteins to biological ageing clocks. Nat Cell Biol 26, 851–858 (2024). https://doi.org/10.1038/s41556-024-01423-w

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