Imperial College London
Alternate

DrHelenaCocheme

Faculty of Medicine, Institute of Clinical Sciences

Honorary Senior Lecturer
 
 
 
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Contact

 

helena.cocheme Website

 
 
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Location

 

4.15ELMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bjedov:2020:10.1371/journal.pgen.1009083,
author = {Bjedov, I and Cocheme, HM and Foley, A and Wieser, D and Woodling, NS and Castillo-Quan, JI and Norvaisas, P and Lujan, C and Regan, J and Toivonen, JM and Murphy, MP and Thornton, J and Kinghorn, KJ and Neufeld, TP and Cabreiro, F and Partridge, L},
doi = {10.1371/journal.pgen.1009083},
journal = {PLoS Genetics},
pages = {1--33},
title = {Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila},
url = {http://dx.doi.org/10.1371/journal.pgen.1009083},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention.
AU  - Bjedov,I
AU  - Cocheme,HM
AU  - Foley,A
AU  - Wieser,D
AU  - Woodling,NS
AU  - Castillo-Quan,JI
AU  - Norvaisas,P
AU  - Lujan,C
AU  - Regan,J
AU  - Toivonen,JM
AU  - Murphy,MP
AU  - Thornton,J
AU  - Kinghorn,KJ
AU  - Neufeld,TP
AU  - Cabreiro,F
AU  - Partridge,L
DO  - 10.1371/journal.pgen.1009083
EP  - 33
PY  - 2020///
SN  - 1553-7390
SP  - 1
TI  - Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1009083
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000595960400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009083
UR  - http://hdl.handle.net/10044/1/85475
VL  - 16
ER  -
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