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Restoring information in aged gene regulatory networks by single knock-ins

Ryan LeFebre1, Tyler Schutt1, Fabrisia Ambrosio2,3, and Andrew Mugler1,*

  • *Contact author: andrew.mugler@pitt.edu
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Phys. Rev. E 114, 044401 – Published 2 October, 2026

DOI: https://doi.org/10.1103/cbwg-5nw6

Abstract

A hallmark of aging is loss of information in gene regulatory networks: gene expression becomes less correlated with biological age. These networks are tightly connected, raising the question of whether information could be restored by perturbing single genes. We develop a simple theoretical framework for information transmission in gene regulatory networks that describes the information gained or lost when a gene is “knocked in” (exogenously expressed). Applying the framework to gene expression data from muscle cells in young and old mice, we find that single knock-ins can restore network information by up to 10%. Our work advances the study of information flow in networks and identifies potential gene targets for rejuvenation.

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Outline

Information

Phys. Rev. E 114, 044401– Published 2 October, 2026
  • Received 7 January 2026
  • Revised 8 July 2026
  • Accepted 11 August 2026
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