Sies · Nature reviews. Molecular cell biology 2020 · narrative review · n=?

Reactive oxygen species (ROS) as pleiotropic physiological signalling agents.

Cited 5176 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic biology without new empirical data or systematic search protocol.

PubMed 32231263 · doi:10.1038/s41580-020-0230-3 · record verified 2026-08-30

What was done

This narrative review summarizes the physiological roles of reactive oxygen species (ROS), specifically hydrogen peroxide (H2O2) and superoxide (O2•-), in redox signaling ('oxidative eustress') versus molecular damage ('oxidative distress'). It surveys enzymatic sources, protein targets, physiological regulation across organ systems, and implications for targeted redox medicine based on published mechanistic and clinical literature.

What was found

The abstract reports no primary quantitative data or statistical analyses. It notes that more than 40 enzymes generate signaling ROS, with H2O2 operating at physiological concentrations in the nanomolar range via specific post-translational protein modifications. It also notes that non-specific scavenging of ROS using low-molecular-mass antioxidants has historically failed to prevent disease initiation or progression in clinical trials.

Why it matters

It establishes that ROS are necessary physiological signaling messengers at nanomolar levels rather than purely destructive metabolic byproducts. This distinction explains why broad-spectrum antioxidant clinical trials largely failed and supports developing targeted redox therapies.

Limits

As a narrative review, it lacks a systematic literature search, pre-specified study selection criteria, and quantitative data synthesis. Findings rely on mechanistic and preclinical models, and no primary human data or specific sample sizes are reported in the abstract.

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