USP-48 and insulin-linked longevity in C. elegans: an abstract-only RNAi screen
In the abstract, a genome-wide double-RNAi screen in C. elegans identified USP-48 as needed for lifespan extension when insulin/IGF-1 signalling is reduced; it acts mainly in the hypodermis and shapes stress-responsive transcription. [1]
Automatic summary · not editorially reviewed
The key findings
Depleting the mitochondrial prohibitin complex shortens lifespan in wild-type C. elegans but extends it in daf-2 insulin/IGF-1 receptor mutants. [1]
A genome-wide double-RNAi screen identified USP-48 as required for lifespan extension under reduced insulin signalling, acting mainly in the hypodermis. [1]
USP-48 cooperates with DVE-1 to regulate the UPR largely independently of ATFS-1 and promotes histone H2B deubiquitination. [1]
The source at a glance
- Study type / format
- Abstract of a genome-wide double-RNAi screen with follow-up experiments in C. elegans
- Population / context
- C. elegans nematodes, including wild-type and daf-2 insulin/IGF-1 receptor mutants
- Summary based on
- Study abstract
- Original publication
- September 30, 2026
Why the screen compared wild-type and daf-2 worms
The abstract states that the mitochondrial prohibitin complex is essential for mitochondrial homeostasis. Its depletion shortens lifespan in wild-type C. elegans but extends it in insulin/IGF-1 receptor daf-2 mutants, which show an attenuated mitochondrial unfolded protein response (UPR). To find regulators of this differential stress response and its role in aging, the authors report conducting the first genome-wide double-RNAi screen in C. elegans.
Supporting source [1]
USP-48, DVE-1 and the hypodermis in the abstract
The screen identified the ubiquitin-specific peptidase USP-48 as a modulator of the UPR, specifically required for lifespan extension under reduced insulin signalling. USP-48 influences mitochondrial structure and function and cooperates with the transcription factor DVE-1 to regulate the UPR largely independently of ATFS-1. Tissue-specific analysis shows USP-48 is required for lifespan primarily in the hypodermis, with a smaller germline contribution, but is dispensable in muscle and intestine. Mechanistically, it promotes histone H2B deubiquitination to shape stress-responsive transcription.
Supporting source [1]
What this abstract does not establish
These are findings in the nematode C. elegans, not evidence of human lifespan effects. The abstract reports a screen and follow-up experiments but gives no sample sizes, follow-up periods or effect sizes, and the full text was not reviewed. The abstract frames ubiquitination as a determinant of metabolism-dependent longevity; this is an association in a model organism, not proof of cause in humans.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings are in C. elegans; no sample sizes, follow-up or effect sizes are reported, and human relevance is not established.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Gordillo-García S, Fernandez-Abascal J, Hernando-Rodríguez B, Rodríguez-Palero MJ, Cantalejo-Carrasco L, Jarit-Cabanillas A, Martínez-Bueno MD, Pérez-Jiménez MM, Clavijo-Bernal EJ, Cambón A, Cases I, Eder M, Artal-Sanz M. · europepmc.org · September 30, 2026