IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction

De-Souza, Evandro A., Cummins, Nadia and Taylor, Rebecca C. ORCID: (2022) IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction. Frontiers in Aging, 3. ISSN 2673-6217

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The proteome of a cell helps to define its functional specialization. Most proteins must be translated and properly folded to ensure their biological function, but with aging, animals lose their ability to maintain a correctly folded proteome. This leads to the accumulation of protein aggregates, decreased stress resistance, and the onset of age-related disorders. The unfolded protein response of the endoplasmic reticulum (UPRER) is a central protein quality control mechanism, the function of which is known to decline with age. Here, we show that age-related UPRER decline in Caenorhabditis elegans occurs at the onset of the reproductive period and is caused by a failure in IRE-1 endoribonuclease activities, affecting both the splicing of xbp-1 mRNA and regulated Ire1 dependent decay (RIDD) activity. Animals with a defect in germline development, previously shown to rescue the transcriptional activity of other stress responses during aging, do not show restored UPRER activation with age. This underlines the mechanistic difference between age-associated loss of UPRER activation and that of other stress responses in this system, and uncouples reproductive status from the activity of somatic maintenance pathways. These observations may aid in the development of strategies that aim to overcome the proteostasis decline observed with aging.

Item Type: Article
Additional Information: Funding: This work has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement Number 894039, and was also supported by the Medical Research Council.
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 12 Jan 2023 09:30
Last Modified: 12 Jan 2023 09:30
DOI: 10.3389/fragi.2022.1044556


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