# Supplement: USING OPTOGENETICS TO DISSECT THE ROLE OF REDOX SIGNALING DURING C. ELEGANS AGING

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $50,000

## Abstract

PROJECT SUMMARY
The model that reactive oxygen species (ROS) cause age-related degeneration has been challenged by the
observation that endogenously produced ROS are essential second messengers sufficient to extend lifespan in
many model organisms. Seemingly contradictory results and regulatory models derived from manipulations of
global ROS levels are commonly framed as the `antioxidant paradox' of aging12. A key observation is that long-
lived mutant animals of several model organisms, including C. elegans, often require ROS for lifespan
extension, which seems contrary to the free radical theory of aging that posits ROS are deleterious. We
propose to address this paradox in the context of C. elegans longevity and aging. We hypothesize that the
location and level of redox signaling is the critical determinant of whether ROS promote lifespan extension or
cause age-related degeneration. To test this hypothesis, we will utilize an innovative new technique,
optogenetic production of ROS, to systematically explore how the location, timing and intensity of intracellular
ROS production affects C. elegans lifespan, healthspan and transcriptional programs. Aim 1 will define the
locations, both at the subcellular and tissue level, that are sufficient for C. elegans lifespan extension. Aim 2
will determine how spatial regulation of ROS production controls activation of lifespan extending transcriptional
programs. The ability to precisely control ROS production with optogenetics will enable us for the first time to
disentangle how redox signaling networks functionally contribute to complex phenotypes such as aging.
Successful completion of these aims will have a significant impact by elucidating the biology of redox signaling
that influences lifespan and suggesting strategies to improve development and application of antioxidants as
possible therapeutics for aging and age-related disease.

## Key facts

- **NIH application ID:** 10142197
- **Project number:** 3R21AG058037-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jason M. Held
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,000
- **Award type:** 3
- **Project period:** 2009-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142197

## Citation

> US National Institutes of Health, RePORTER application 10142197, Supplement: USING OPTOGENETICS TO DISSECT THE ROLE OF REDOX SIGNALING DURING C. ELEGANS AGING (3R21AG058037-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142197. Licensed CC0.

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