Evidence map›Paper›PMID 42021510›Full record

ArticleAging cell2026

Fasting and Caloric Restriction Activate an ADIOL-NHR-91-Kynurenine Pathway Signaling Axis to Promote Healthspan.

Ana Guijarro-Hernández, Shinja Yoo, George A Lemieux, Sena Komatsu, Abdullah Q Latiff, Rishika R Patil, Kaveh Ashrafi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Ana Guijarro-HernándezDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0003-1061-7744
Shinja YooDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
George A LemieuxDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Sena KomatsuDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Abdullah Q LatiffDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Rishika R PatilDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Kaveh AshrafiDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Linking metabolism, neural function, and agingR01AG046400 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHRAFI, KAVEH · 2014 to 2023
$4.3M
Role of the steroid hormone ADIOL in learning and memory, aging, and neurodegenerationRF1AG068194 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHRAFI, KAVEH · 2021 to 2021
$1.7M
NIA NIH HHS R01 AG046400NIA NIH HHS RF1 AG068194NIH HHS P40 OD010440NIH HHS R01AG046400NIH HHS RF1AG068194UCSF Program for Breakthrough Biomedical Research
6 · The paper itself

Abstract

The steroid hormone 5-androstene-3β,17β-diol (ADIOL) was discovered nearly a century ago in humans, yet its physiological functions have remained poorly understood. Using C. elegans, we identify ADIOL as essential for several pro-healthspan effects of fasting and caloric restriction (CR). These dietary restriction regimens activate an ADIOL-NHR-91-kynurenic acid signaling axis, partly through transcriptional programs associated with ADIOL biosynthesis. Within this axis, ADIOL acts through NHR-91, a C. elegans homolog of estrogen receptor β, to reduce levels of kynurenic acid, a neuromodulatory metabolite, thereby enhancing healthspan. Critically, ADIOL does not extend lifespan, indicating its healthspan benefits are independent of longevity, and even late-life supplementation is effective. Collectively, this work establishes ADIOL as a physiological link between metabolic cues and neural function, promoting health during aging via the kynurenine pathway. Given that in mammals ADIOL similarly is a ligand for estrogen receptor β and the kynurenine pathway influences neuroprotection mechanisms, ADIOL may represent an evolutionarily conserved signal by which dietary interventions enhance healthy aging.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsCaloric RestrictionFastingKynurenineSignal TransductionAnimalsHumansLongevityCaenorhabditis elegans ProteinsKynurenineandrostenediolcaloric restrictionestrogen receptor betafastinghealthy agingkynurenic acidlearningmovementsteroids

Identifiers

PMID42021510
PMCPMC13103470

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.