title: Glucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice.
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.
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Missios
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Guachalla
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: von Figura
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg.
authors.forename: Andre
authors.initials: A
authors.lastname: Wegner
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Sundaram Reddy
authors.initials: SR
authors.lastname: Chakkarappan
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg.
authors.forename: Tina
authors.initials: T
authors.lastname: Binz
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Gompf
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Hartleben
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Burkhalter
authors.affiliation: Institute for Genetics, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Street 47A, 50674 Cologne, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Wulff
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
authors.forename: Cagatay
authors.initials: C
authors.lastname: Günes
authors.affiliation: Institute of Epidemiology, Ingolstädter Landstrasse 1, 85764 Munich/Neuherberg, Germany.
authors.forename: Rui Wang
authors.initials: RW
authors.lastname: Sattler
authors.affiliation: Cooperation Group of the Leibniz Institute for Age Research-Fritz-Lipmann-Institute (FLI) Jena with the University of Ulm, 89081 Ulm, Germany.
authors.forename: Zhangfa
authors.initials: Z
authors.lastname: Song
authors.affiliation: Institute of Epidemiology, Ingolstädter Landstrasse 1, 85764 Munich/Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Klaus
authors.affiliation: Department of Internal Medicine I, University of Ulm, 89081 Ulm, Germany.
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Böhm
authors.affiliation: Institute for Genetics, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Zülpicher Street 47A, 50674 Cologne, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Wenz
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 7, avenue des Hauts-Fourneaux, Esch-Belval L-4362, Luxembourg.
authors.forename: Karsten
authors.initials: K
authors.lastname: Hiller
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany.
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002151:Calorimetry; D003433:Crosses, Genetic; D004249:DNA Damage; D004032:Diet; D004734:Energy Metabolism; D005347:Fibroblasts / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000737:chemistry*; D006019:Glycolysis; D006579:Heterozygote; D006706:Homeostasis; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010100:Oxygen / Q000737:chemistry; D020123:Sirolimus / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D010100:Oxygen; D020123:Sirolimus