XXBP-1 Is a cell-nonautonomous regulator of stress resistance and longevity

Taylor, Rebecca C. and Dillin, Andrew (2013) XXBP-1 Is a cell-nonautonomous regulator of stress resistance and longevity. Cell, 153 (7). pp. 1435-1447. ISSN 0092-8674

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Abstract

The ability to ensure proteostasis is critical for maintaining proper cell function and organismal viability but is mitigated by aging. We analyzed the role of the endoplasmic reticulum unfolded protein response (UPRER) in aging of C. elegans and found that age-onset loss of ER proteostasis could be reversed by expression of a constitutively active form of XBP-1, XBP-1s. Neuronally derived XBP-1s was sufficient to rescue stress resistance, increase longevity, and activate the UPRER in distal, non-neuronal cell types through a cell-nonautonomous mechanism. Loss of UPR ER signaling components in distal cells blocked cell-nonautonomous signaling from the nervous system, thereby blocking increased longevity of the entire animal. Reduction of small clear vesicle (SCV) release blocked nonautonomous signaling downstream of xbp-1s, suggesting that the release of neurotransmitters is required for this intertissue signaling event. Our findings point toward a secreted ER stress signal (SERSS) that promotes ER stress resistance and longevity. PaperFlick

Item Type:	Article
Uncontrolled Keywords:	biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	13 Feb 2025 17:30
Last Modified:	16 Feb 2025 07:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98490
DOI:	10.1016/j.cell.2013.05.042

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