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Updated: Jul 18, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins
Ala Berdichevsky1, Leonard Guarente
1Department of Biology, Massachusetts Insitute of Technology, Cambridge, Massachusetts 02139, USA.
Abstract:
A conserved sir2 deacetylase gene can determine longevity of yeast, flies and worms. Recently we have reported a molecular mechanism of action of the C. elegans homologue sir-2.1. Our study revealed a novel stress-dependent pathway for lifespan determination in which SIR-2.1 binds to 14-3-3 proteins and a forkhead transcription factor DAF-16 to activate transcription of DAF-16 target genes. DAF-16 has long been known as a central protein in the regulation of lifespan that interfaces with multiple pathways. Recent studies by us and other laboratories suggest that DAF-16 requires co-factors for full activity. In this prospective we review recent literature highlighting the role of SIR-2.1, 14-3-3 and other DAF-16 co-factors in DAF-16 activation.
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