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.
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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.
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