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Testing the mitochondrial theory of ageing

Objective

The mitochondria theory of ageing proposes that the accumulation of somatic mutations in mitochondria DNA during life results in a progressive decline in energetic function and eventual cellular and organism senescence. We propose to test this idea directly, by engineering and expressing a version of the mitochondria DNA polymerise POLG that lacks proofreading exonuclease activity, and hence results in the rapid accumulation of medina mutations. This medina matador will be created and tested in parallel in four model systems: yeast, the mouse, cultured human cells and the fruit fly Drosophilae. The phenotypic consequences of an enhanced rate of accumulation of medina mutations will be investigated via studies of cellular bioenergetics function, ageing-related physiological decline and tissue degeneration, alterations in the pattern of gene expression, and overall lifespan.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY OF TAMPERE
Address
6,Lenkkeilijänkatu 6
33014 Tampere
Finland

Participants (4)

ASTRA ZENECA AB
Sweden
Address
Soedertaelje
15185 Jaerna
KAROLINSKA INSTITUTE
Sweden
Address
Karolinska Hospital
171 76 Stockholm
UNIVERSIDAD AUTONOMA DE MADRID
Spain
Address
Arzobispo Morcillo N2
28029 Madrid
UNIVERSITE CATHOLIQUE DE LOUVAIN
Belgium
Address
Place Croix Du Sud 2/19
1348 Louvain-la-neuve