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Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp11

Martinez Corrales, Guillermo; Li, Mengjia; Svermova, Tatiana; Goncalves, Alex; Dobson, Adam; Voicu, Diana; Southall, Tony; (2022) Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp11. Nature Aging , 2 pp. 1176-1190. 10.1038/s43587-022-00312-x. Green open access

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Abstract

A transient, homeostatic transcriptional response can result in transcriptional memory, programming subsequent transcriptional outputs. Transcriptional memory has great but unappreciated potential to alter animal aging as animals encounter a multitude of diverse stimuli throughout their lifespan. Here we show that activating an evolutionarily conserved, longevity-promoting transcription factor, dFOXO, solely in early adulthood of female fruit flies is sufficient to improve their subsequent health and survival in midlife and late life. This youth-restricted dFOXO activation causes persistent changes to chromatin landscape in the fat body and requires chromatin remodelers such as the SWI/SNF and ISWI complexes to program health and longevity. Chromatin remodeling is accompanied by a long-lasting transcriptional program that is distinct from that observed during acute dFOXO activation and includes induction of Xbp1. We show that this later-life induction of Xbp1 is sufficient to curtail later-life mortality. Our study demonstrates that transcriptional memory can profoundly alter how animals age.

Type: Article
Title: Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp11
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s43587-022-00312-x
Publisher version: https://doi.org/10.1038/s43587-022-00312-x
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10159417
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