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Role of mitochondrial disfunction in the energy collapse associated to aging and frailty. Basci an translational aspects

20th national competition for scientific and technical research

Aging and neurodegenerative diseases

Senior Researcher : José Viña Ribes

Research Centre or Institution : Universidad de Valencia.

Abstract

This research project was conceived to tackle three major aims.  The first was to determine the expression of the genes BCL-xL and AHR and their mitochondrial-related pathways in frail persons.  The second was to determine frailty and to perform transcriptomics and mitochondrial function of skeletal muscle in mouse models related to the genes that we have just mentioned above and finally to determine the molecular mechanisms involved in each of the models, but using in vitro cell cultures.

In this first year of the project we have tackled the three aims using the following approaches:

For the first aim, we have started recruiting individuals, both frail and non-frail, as well as offspring of centenarians to determine the BCL-xL and AHR in blood cells of these individuals.  Regarding the second aim, we have started the colonies of BCL-xL overexpressing animals to be studied in the second year of this research project and compare them with controls. We have been able to analyse all the control mice (from colonies that we had in previous studies) and will compare them with BCL- xL overexpressing animals to test if they are less frail than controls. 

Regarding the third aim, we have set up a method to determine bioenergenics of C2C12 cells using the seahorse apparatus. Preliminary results shown in the Figure indicate that mitochondrial function in preserved in old nicotinamide riboside- supplemented old animals. 

All the results indicate that attacking the problem of age- associated energy collapse by promoting maintenance of mitochondria from different standpoints, from the human to the experimental animal to the cell in culture is a fruitful approach to eventually obtain significant recommendations to improve the quality of life of the old human population. 

 

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Communications at international conferences 1

 

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