气候变化领域集成服务门户(CCPortal): Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system

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DOI	10.1073/pnas.2011491118
	Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system
	Bolukbasi E.; Woodling N.S.; Ivanov D.K.; Adcott J.; Foley A.; Rajasingam A.; Gittings L.M.; Aleyakpo B.; Niccoli T.; Thornton J.M.; Partridge L.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila. Starting from published single-cell transcriptomic data, we report that forkhead (FKH) is endogenously expressed in neurons, whereas forkhead-box-O (FOXO) is expressed in glial cells. Accordingly, we find that neuronal FKH and glial FOXO exert independent prolongevity effects. We have further explored the role of neuronal FKH in a model of Alzheimer’s disease-associated neuronal dysfunction, where we find that increased neuronal FKH preserves behavioral function and reduces ubiquitinated protein aggregation. Finally, using transcriptomic profiling, we identify Atg17, a member of the Atg1 autophagy initiation family, as one FKH-dependent target whose neuronal overexpression is sufficient to extend healthy lifespan. Taken together, our results underscore the importance of cell type-specific mapping of TF activity to preserve healthy function with age. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aging; Alzheimer’s disease; Glia; Neurons; Transcription factors
语种	英语
scopus关键词	forkhead transcription factor; adult; Alzheimer disease; animal experiment; Article; cells by body anatomy; controlled study; Drosophila; female; gene expression; gene identification; glia cell; lifespan; nervous system; nonhuman; priority journal; protein aggregation; protein expression; transcriptomics; ubiquitination
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180551
作者单位	Institute of Healthy Ageing, University College London, London, WC1E 6BT, United Kingdom; Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, United Kingdom; European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, CB10 1SD, United Kingdom; UK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, United Kingdom; Department of Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany
推荐引用方式 GB/T 7714	Bolukbasi E.,Woodling N.S.,Ivanov D.K.,et al. Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system[J],2021,118(8).
APA	Bolukbasi E..,Woodling N.S..,Ivanov D.K..,Adcott J..,Foley A..,...&Partridge L..(2021).Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Bolukbasi E.,et al."Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).