Show simple item record

dc.contributor.author
Ewald, Collin
dc.contributor.author
Marfil, Vanessa
dc.contributor.author
Li, Chris
dc.date.accessioned
2019-09-09T11:12:46Z
dc.date.available
2017-06-12T11:40:22Z
dc.date.available
2019-09-09T11:12:46Z
dc.date.issued
2016-12
dc.identifier.issn
1474-9718
dc.identifier.issn
1474-9728
dc.identifier.issn
1474-9726
dc.identifier.other
10.1111/acel.12509
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/119910
dc.identifier.doi
10.3929/ethz-b-000119910
dc.description.abstract
Alzheimer's disease (AD) is an age‐associated disease. Mutations in the amyloid precursor protein (APP) may be causative or protective of AD. The presence of two functionally redundant APP‐like genes (APLP1/2) has made it difficult to unravel the biological function of APP during aging. The nematode Caenorhabditis elegans contains a single APP family member, apl‐1. Here, we assessed the function of APL‐1 on C. elegans’ lifespan and found tissue‐specific effects on lifespan by overexpression of APL‐1. Overexpression of APL‐1 in neurons causes lifespan reduction, whereas overexpression of APL‐1 in the hypodermis causes lifespan extension by repressing the function of the heterochronic transcription factor LIN‐14 to preserve youthfulness. APL‐1 lifespan extension also requires signaling through the FOXO transcription factor DAF‐16, heat‐shock factor HSF‐1, and vitamin D‐like nuclear hormone receptor DAF‐12. We propose that reinforcing APL‐1 expression in the hypodermis preserves the regulation of heterochronic lin‐14 gene network to improve maintenance of somatic tissues via DAF‐16/FOXO and HSF‐1 to promote healthy aging. Our work reveals a mechanistic link of how a conserved APP‐related protein modulates aging.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley-Blackwell
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Alzheimer's disease
en_US
dc.subject
APL-1
en_US
dc.subject
APP
en_US
dc.subject
FOXO transcription factor DAF-16
en_US
dc.subject
Heat-shock factor HSF-1
en_US
dc.subject
Heterochronic gene LIN-14
en_US
dc.subject
Lifespan
en_US
dc.subject
Vitamin D-like nuclear hormone receptor DAF-12
en_US
dc.title
Alzheimer-related protein APL-1 modulates lifespan through heterochronic gene regulation in Caenorhabditis elegans
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-08-24
ethz.journal.title
Aging Cell
ethz.journal.volume
15
en_US
ethz.journal.issue
6
en_US
ethz.journal.abbreviated
Aging cell
ethz.pages.start
1051
en_US
ethz.pages.end
1062
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.identifier.nebis
004513522
ethz.publication.place
s.l.
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09598 - Ewald, Collin Y. / Ewald, Collin Y.
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09598 - Ewald, Collin Y. / Ewald, Collin Y.
ethz.date.deposited
2017-06-12T11:46:07Z
ethz.source
ECIT
ethz.identifier.importid
imp593654aabc42450586
ethz.ecitpid
pub:181956
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T12:07:20Z
ethz.rosetta.lastUpdated
2022-03-28T23:36:44Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Alzheimer-related%20protein%20APL-1%20modulates%20lifespan%20through%20heterochronic%20gene%20regulation%20in%20Caenorhabditis%20elegans&rft.jtitle=Aging%20Cell&rft.date=2016-12&rft.volume=15&rft.issue=6&rft.spage=1051&rft.epage=1062&rft.issn=1474-9718&1474-9728&1474-9726&rft.au=Ewald,%20Collin&Marfil,%20Vanessa&Li,%20Chris&rft.genre=article&rft_id=info:doi/10.1111/acel.12509&
 Search print copy at ETH Library

Files in this item

Thumbnail

Publication type

Show simple item record