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Nat Commun. 2014 Sep 18;5:4924. doi: 10.1038/ncomms5924.

Glucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice.

Author information

1
Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
2
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg.
3
Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
4
Institute for Genetics, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Street 47A, 50674 Cologne, Germany.
5
Institute of Epidemiology, Ingolstädter Landstrasse 1, 85764 Munich/Neuherberg, Germany.
6
German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
7
Department of Internal Medicine I, University of Ulm, 89081 Ulm, Germany.

Abstract

DNA damage and telomere dysfunction shorten organismal lifespan. Here we show that oral glucose administration at advanced age increases health and lifespan of telomere dysfunctional mice. The study reveals that energy consumption increases in telomere dysfunctional cells resulting in enhanced glucose metabolism both in glycolysis and in the tricarboxylic acid cycle at organismal level. In ageing telomere dysfunctional mice, normal diet provides insufficient amounts of glucose thus leading to impaired energy homeostasis, catabolism, suppression of IGF-1/mTOR signalling, suppression of mitochondrial biogenesis and tissue atrophy. A glucose-enriched diet reverts these defects by activating glycolysis, mitochondrial biogenesis and oxidative glucose metabolism. The beneficial effects of glucose substitution on mitochondrial function and glucose metabolism are blocked by mTOR inhibition but mimicked by IGF-1 application. Together, these results provide the first experimental evidence that telomere dysfunction enhances the requirement of glucose substitution for the maintenance of energy homeostasis and IGF-1/mTOR-dependent mitochondrial biogenesis in ageing tissues.

PMID:
25233189
PMCID:
PMC4199114
DOI:
10.1038/ncomms5924
[Indexed for MEDLINE]
Free PMC Article

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