COMPLEXI&AGING

Modulation of mitochondrial complex I as a strategy to increase lifespan and prevent age-related diseases

Coordinatore	UNIVERSITY OF NEWCASTLE UPON TYNE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	1˙491˙600 €
EC contributo	1˙491˙600 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2010-StG_20091118
Funding Scheme	ERC-SG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-02-01   -   2016-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	TAMPEREEN YLIOPISTO  Organization address address: Kalevantie 4 city: TAMPERE postcode: 33014 contact info Titolo: Ms. Nome: Hannele Cognome: Auffermann Email: send email Telefono: 358405000000 Fax: 358336000000	FI (TAMPERE)	beneficiary	813˙423.14
2	UNIVERSITY OF NEWCASTLE UPON TYNE  Organization address address: Kensington Terrace 6 city: NEWCASTLE UPON TYNE postcode: NE1 7RU contact info Titolo: Dr. Nome: Alberto Cognome: Sanz Montero Email: send email Telefono: +44 1912081221 Fax: +44 1912081301	UK (NEWCASTLE UPON TYNE)	hostInstitution	678˙176.86
3	UNIVERSITY OF NEWCASTLE UPON TYNE  Organization address address: Kensington Terrace 6 city: NEWCASTLE UPON TYNE postcode: NE1 7RU contact info Titolo: Mrs. Nome: Fiona Cognome: Airey Email: send email Telefono: +44 1912824515	UK (NEWCASTLE UPON TYNE)	hostInstitution	678˙176.86

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 Obiettivo del progetto (Objective)

Nowadays, ageing is one of the main problems in Western society. The increase in the percentage of elderly people serves to strain the Social Security to the point of bankruptcy. The only way to alleviate the suffering caused by age-related degenerative disease is to fully understand the underlying forces which drive ageing and design strategies to delay it. Mitochondria are considered as central modulators of longevity in different species. It has been proposed that free radicals cause the accumulation of oxidative damage and as a result ageing. In accordance with this, production of Reactive Oxygen Species (ROS) by complex I negatively correlates with longevity. However, the overexpression of antioxidants or the reduction of ROS levels does not increase lifespan. These contradictory data can only be reconciled if complex I is modulating longevity through a ROS independent mechanism. We have expressed the alternative internal NADH dehydrogenase 1 (NDI1) from Saccharomyces cerevisiae in Drosophila melanogaster. The expression of NDI1 does not change the level of ROS but increases both the ratio of NAD/NADH and Drosophila longevity. The main objective of this proposal is to study the mechanisms by which complex I regulates longevity. My general hypothesis is that complex I regulates longevity through a ROS independent mechanism. I propose that complex I controls the cellular levels of NAD/NADH, keeping their levels at an equilibrium that favours the optimal functioning of the cell. When the ratio is moved towards NADH ageing is promoted, whereas when it is moved towards NAD pro-survival pathways are activated. I proposed two specific mechanisms downstream of complex I that promote cellular longevity or senescence: 1) activation of sirtuins, which would increase genome stability and 2) reduction of methylglyoxal generation, which would decrease the accumulation of cellular garbarge .