Dietary thiols accelerate aging of C. elegans

Area of Science:

• Cellular biology
• Aging research
• Nutritional science

Background:

• Glutathione (GSH) is a primary cellular antioxidant crucial for neutralizing reactive oxygen species (ROS).
• N-acetyl cysteine (NAC), a GSH precursor, and GSH itself are popular dietary supplements due to their antioxidant properties.
• The long-term impact of exogenous GSH or NAC on healthy aging remains largely unexamined.

Purpose of the Study:

• To investigate the effects of chronic glutathione (GSH) and N-acetyl cysteine (NAC) administration on aging in a model organism.
• To explore the consequences of modulating dietary thiol intake on lifespan and cellular stress responses.
• To determine the benefits of endogenous GSH synthesis versus exogenous antioxidant supplementation for healthy individuals.

Main Methods:

• Utilized Caenorhabditis elegans (C. elegans) as a model organism for studying aging.
• Administered chronic glutathione (GSH) or N-acetyl cysteine (NAC) to young and aged C. elegans.
• Analyzed global gene expression, skn-1-mediated transcription, lifespan, unfolded protein response activation, and proteotoxic stress resistance.
• Investigated the effects of limiting dietary thiols, including microbial contributions.

Main Results:

• Chronic GSH or NAC administration perturbed global gene expression and accelerated aging in C. elegans.
• Supplementation inhibited skn-1-mediated transcription, a key regulator of stress resistance and longevity.
• Limiting dietary thiols extended lifespan and enhanced proteotoxic stress resistance via the unfolded protein response in both worms and human cells.

Conclusions:

• Excessive dietary antioxidants like GSH and NAC may be detrimental to healthy aging.
• Relying on intrinsic GSH biosynthesis, which adapts to cellular redox status, is advantageous for promoting longevity.
• Pharmacological restriction of GSH activates protective cellular stress responses, highlighting the importance of balanced antioxidant levels.