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Dietary restriction promotes neuronal resilience via ADIOL
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
Fasting boosts steroid hormone ADIOL (5-androstene-3β,17β-diol) synthesis, which protects the nervous system and improves healthspan. Enhancing ADIOL signaling may offer therapeutic benefits for age-related neurodegeneration.
Area of Science:
- Endocrinology
- Neuroscience
- Aging Research
Background:
- The physiological roles of the steroid hormone 5-androstene-3β,17β-diol (ADIOL) are not well understood.
- Dietary restriction, including fasting and caloric restriction, is known to promote healthspan.
Purpose of the Study:
- To investigate the role of ADIOL in mediating the health benefits of dietary restriction.
- To explore ADIOL's potential as a neuroprotective agent.
Main Methods:
- Studied the effect of fasting and caloric restriction on ADIOL biosynthesis genes.
- Investigated ADIOL's impact on kynurenic acid levels in the nervous system using C. elegans models.
- Assessed healthspan indicators and cellular stress responses.
Main Results:
- Fasting and caloric restriction upregulate genes promoting ADIOL biosynthesis.
- ADIOL reduces neurotoxic kynurenic acid levels, requiring NHR-91 in RIM neurons.
- Enhanced ADIOL signaling improves healthspan and suppresses APOE4-induced cellular stress.
Conclusions:
- ADIOL mediates the neuroprotective and pro-healthspan effects of dietary restriction.
- ADIOL signaling is a promising therapeutic target for age-related neurodegenerative diseases and healthspan extension.
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