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The Information Theory of Aging

Abstract

Information storage and retrieval is essential for all life. In biology, information is primarily stored in two distinct ways: the genome, comprising nucleic acids, acts as a foundational blueprint and the epigenome, consisting of chemical modifications to DNA and histone proteins, regulates gene expression patterns and endows cells with specific identities and functions. Unlike the stable, digital nature of genetic information, epigenetic information is stored in a digital–analog format, susceptible to alterations induced by diverse environmental signals and cellular damage. The Information Theory of Aging (ITOA) states that the aging process is driven by the progressive loss of youthful epigenetic information, the retrieval of which via epigenetic reprogramming can improve the function of damaged and aged tissues by catalyzing age reversal.

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Fig. 1: The ITOA.
Fig. 2: The epigenetic landscape of development, aging and rejuvenation.
Fig. 3: The rejuvenation of old and damaged cells via epigenetic reprogramming.

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Acknowledgements

We thank E. Smith for figure illustrations and R. Rogers-Hammond and M. LaPlante for manuscript advice. Y.R.L. was supported by postdoctoral fellowships from Glenn/AFAR (by Michael Shen, MIT'13) and the Life Sciences Research Foundation (by Lei-Luo Life Science Fund). X.T. was supported by a NIH/NIA award K99AG068303. This work was also funded by NIH/NIA R01AG019719, Harvard Medical School Epigenetics Grants, gifts from M. Chambers, R. Rosenkrantz, T. Robbins, P. Diamandis, S. Aoki, D. and S. Hoff, and the Glenn Foundation for Medical Research to D.A.S.

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Y.R.L., X.T. and D.A.S. wrote this Perspective.

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Correspondence to David A. Sinclair.

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Y.R.L., D.A.S. and X.T. are inventors on patent applications licensed to Life Biosciences, a company developing epigenetic reprogramming-based therapies, in which Y.R.L. and D.A.S. have equity. Complete details of all relationships for profit and not-for-profit for D.A.S. can be found in the Supplementary Information.

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Lu, Y.R., Tian, X. & Sinclair, D.A. The Information Theory of Aging. Nat Aging 3, 1486–1499 (2023). https://doi.org/10.1038/s43587-023-00527-6

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