What this means
Researchers turned down autophagy genes in tiny worms and checked how long the worms lived under different settings. The results changed with temperature, worm type, and gene, so this preprint does not clearly show how much autophagy matters for long life.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- C. elegans worms (roundworms); lab study not yet checked by other scientists
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- Effects of knockdown of autophagy pathway genes on C. elegans longevity are highly condition dependent
- Authors
- Hsiung, K. C., Chapman, H., Wei, X. et al.
- Journal
- bioRxiv (preprint, not yet peer reviewed)
- Published
- Oct 14, 2026
- Study type
- Preprint
Abstract
Autophagy is proposed to protect against aging by clearing damaged cellular constituents. In line with this several life-extending interventions in model organisms show some degree of autophagy dependence. In C. elegans, inhibiting autophagy can shorten, lengthen or have no effect on lifespan. Differences between published findings likely reflect variability in experimental conditions. Here we investigate the condition dependence of effects on lifespan of RNA-mediated interference (RNAi) knockdown of autophagy pathway components. Effects on interventions causing a strong Age (increased lifespan) phenotype were examined, mainly mutation of daf-2 (insulin/IGF-1 receptor). Factors varied included daf-2 mutant allele class, atg gene and temperature. Effects on lifespan of atg RNAi proved to be highly condition dependent. Notably, for most atg genes tested lifespan was not usually reduced more in the long-lived mutant than in the wild-type control. Greater suppression was seen at 20{ring}C for certain atg genes with daf-2(e1368) but not daf-2(e1370). At 25{ring}C, little reduction in lifespan was seen. However, atg-18 knockdown behaved differently, suppressing daf-2 Age under all conditions, suggesting possible pleiotropic action. Condition dependent effects were also seen with respect to glp-1 (reduced germline development) Age. Furthermore, presence of 5-fluoro-2'-deoxyuridine (FUDR) at a high concentration caused knockdown of several atg genes to increase lifespan in wild-type C. elegans. Thus, depending on experimental conditions, atg knockdown can increase, decrease or have no effect on daf-2 Age. The lack of suppression of daf-2 Age by atg RNAi under most conditions questions the importance of autophagy for this phenotype. Moreover, condition dependence of effects creates a risk of possible condition selection bias.
Hsiung, K. C., Chapman, H., Wei, X. et al. Effects of knockdown of autophagy pathway genes on C. elegans longevity are highly condition dependent. bioRxiv. 2026. doi:10.1101/2025.07.28.667102. https://doi.org/10.1101/2025.07.28.667102