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Related Experiment Video

Updated: Apr 23, 2026

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
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Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.

Amit Kumar Sahu1,2, Alberto Minetti1,3, Domenico Di Fraia1,2

  • 1Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.

Nature Communications
|April 21, 2026
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Summary
This summary is machine-generated.

Aging impairs brain deubiquitylating enzymes (DUBs), crucial for protein balance. Antioxidants restore DUB activity, suggesting this decline is an early, reversible factor in brain aging.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Aging Research

Background:

  • The ubiquitin-proteasome system maintains neuronal proteostasis but declines with age.
  • The impact of aging on deubiquitylating enzymes (DUBs) in the vertebrate brain is not well understood.

Purpose of the Study:

  • To investigate how aging affects the activity of deubiquitylating enzymes (DUBs) in the brain.
  • To identify specific DUBs affected by aging and the underlying mechanisms.

Main Methods:

  • Activity-based proteomics was employed to profile cysteine protease DUBs in aging mouse and killifish brains.
  • Oxidative stress and antioxidant treatments (NACET) were used to assess DUB function.
  • Experiments in human iPSC-derived neurons and temporal analysis in mice were conducted.

Main Results:

  • A subset of DUBs showed decreased catalytic activity with age, independent of protein abundance.
  • Oxidative stress impaired DUB function via thiol oxidation; NACET restored activity in aged brains.
  • DUB inhibition preceded proteasome decline in aging mouse brains, and partially mimicked age-related ubiquitylation changes.

Conclusions:

  • Redox-sensitive DUBs lose activity during brain aging.
  • Impaired deubiquitylation is an early, potentially reversible driver of proteostasis decline in the aging brain.