Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodelling and Xbp1

Martínez Corrales, G., Li, M., Svermova, T., Goncalves, A., Voicu, D., Dobson, A. J. , Southall, T. D. and Alic, N. (2022) Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodelling and Xbp1. Nature Aging, 2(12), pp. 1176-1190. (doi: 10.1038/s43587-022-00312-x) (PMID:37118537)

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 ageing 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 mid- and late life. This youth-restricted dFOXO activation causes persistent changes to chromatin landscape in the fat body and requires chromatin remodellers such as the SWI/SNF and ISWI complexes to program health and longevity. Chromatin remodelling is accompanied by a long-lasting transcriptional programme that is distinct from that observed during acute dFOXO activation and includes induction of We show that this later-life induction of is sufficient to curtail later-life mortality. Our study demonstrates that transcriptional memory can profoundly alter how animals age.

• Item Type: Articles
• Keywords: Drosophila, metabolism, physiological programming, dFOXO, Xbp1, chromatin remodelling, Transcriptional memory, ageing, gene regulation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dobson, Dr Adam
• Authors: Martínez Corrales, G., Li, M., Svermova, T., Goncalves, A., Voicu, D., Dobson, A. J., Southall, T. D., and Alic, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nature Aging
• Publisher: Nature Research
• ISSN: 2662-8465
• ISSN (Online): 2662-8465
• Published Online: 01 December 2022