Disruption of the insulin/IGF-1 signaling pathway in Caenorhabditis elegans dramatically increases male longevity and enhances reproductive health late in life

Al-Saadi RS, Lewack HB, Phillips PC · 2026 · Aging (Albany NY) · Atlas ID ALS2026

What this study shows

Ubiquitous auxin-inducible degradation of the DAF-2/IGF-1 receptor in C. elegans males increases median lifespan by more than 440% — among the largest lifespan extensions reported for a single intervention — and prolongs male reproductive function late in life. Notably, degrading DAF-2 specifically in the male germline shortened lifespan, the opposite of its effect in hermaphrodites, underlining that pro-longevity nutrient-sensing interventions can act in a sex- and tissue-dependent way.

Abstract

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Males and females are known to have dramatically different health and lifespan trajectories, but the underlying basis for these differences is yet to be fully elucidated. In the nematode model system, most aging studies have been conducted with hermaphrodites, and little is known about male-specific responses to pro-longevity mutations. Several previous studies have used the auxin-inducible degron system to degrade the DAF-2/IGF-1 receptor in hermaphrodites, finding that both ubiquitous and tissue-specific degradation can extend lifespan.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: C. elegans (males; auxin-inducible degron degradation of DAF-2/IGF-1 receptor)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	C. elegans (males; auxin-inducible degron degradation of DAF-2/IGF-1 receptor)
Journal	Aging (Albany NY)
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.18632/aging.206411 · PMID 42641111

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Auxin-inducible degron degradation of the DAF-2/IGF-1 receptor, ubiquitous or germline-specific
Target	Insulin/IGF-1 receptor signalling (DAF-2)
Model	Caenorhabditis elegans, males
Effect	Ubiquitous DAF-2 degradation raised male median lifespan by more than 440% and prolonged late-life reproductive function, while germline-specific degradation shortened male lifespan.

In the Atlas

Cite this paper

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Al-Saadi, R. S., Lewack, H. B., & Phillips, P. C. (2026). Disruption of the insulin/IGF-1 signaling pathway in Caenorhabditis elegans dramatically increases male longevity and enhances reproductive health late in life. Aging (Albany NY). https://doi.org/10.18632/aging.206411

@article{ALS2026,
  author       = {Al-Saadi, R. S. and Lewack, H. B. and Phillips, P. C.},
  title        = {{Disruption of the insulin/IGF-1 signaling pathway in Caenorhabditis elegans dramatically increases male longevity and enhances reproductive health late in life}},
  journal      = {Aging (Albany NY)},
  year         = {2026},
  doi          = {10.18632/aging.206411},
  note         = {PMID: 42641111},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ALS2026) [Data set]. https://mtor-atlas.org/study/ALS2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ALS2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ALS2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ALS2026/},
  doi          = {10.5281/zenodo.22059963}
}

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