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Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50114

Brink,  Thore C.
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50133

Demetrius,  Lloyd
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

Adjaye,  James A.
Max Planck Society;

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Zitation

Brink, T. C., Demetrius, L., Lehrach, H., & Adjaye, J. A. (2008). Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging. Biogerontology. doi:10.1007/s10522-008-9197-8.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-7EAA-F
Zusammenfassung
Individual differences in the rate of aging are determined by the efficiency with which an organism transforms resources into metabolic energy thus maintaining the homeostatic condition of its cells and tissues. This observation has been integrated with analytical studies of the metabolic process to derive the following principle: The metabolic stability of regulatory networks, that is the ability of cells to maintain stable concentrations of reactive oxygen species (ROS) and other critical metabolites is the prime determinant of life span. The metabolic stability of a regulatory network is determined by the diversity of the metabolic pathways or the degree of connectivity of genes in the network. These properties can be empirically evaluated in terms of transcriptional changes in gene expression. We use microarrays to investigate the age-dependence of transcriptional changes of genes in the insulin signaling, oxidative phosphorylation and glutathione metabolism pathways in mice. Our studies delineate age and tissue specific patterns of transcriptional changes which are consistent with the metabolic stability–longevity principle. This study, in addition, rejects the free radical hypothesis which postulates that the production rate of ROS, and not its stability, determines life span.