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Tipping the metabolic scales towards increased longevity in mammals

Abstract

A hallmark of ageing is dysfunction in nutrient signalling pathways that regulate glucose homeostasis, negatively affecting whole-body energy metabolism and ultimately increasing the organism's susceptibility to disease. Maintenance of insulin sensitivity depends on functional mitochondrial networks, but is compromised by alterations in mitochondrial energy metabolism during ageing. Here we discuss metabolic paradigms that influence mammalian longevity, and highlight recent advances in identifying fundamental signalling pathways that influence metabolic health and ageing through mitochondrial perturbations.

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Figure 1: Metabolic flexibility controls healthspan and lifespan.
Figure 2: Effect of ageing on mitochondrial function.

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Acknowledgements

We apologize to our colleagues for omitting numerous references due to space limitations. We thank Carsten Merkwirth and Kristen Berendzen for their helpful comments on the manuscript. C.E.R is supported by the American Diabetes Association Pathway to Stop Diabetes Grant 1-15-INI-12.

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Riera, C., Dillin, A. Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol 17, 196–203 (2015). https://doi.org/10.1038/ncb3107

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