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

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.