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Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
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Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis.

Jorge Iván Castillo-Quan1, Li Li2, Kerri J Kinghorn2

  • 1Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann Strasse 9-b, 50931 Köln, Germany; Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.

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|April 13, 2016
PubMed
Summary

Lithium, an approved drug, extends lifespan and healthspan in fruit flies by inhibiting glycogen synthase kinase-3 (GSK-3) and activating nuclear factor erythroid 2-related factor (NRF-2). This discovery offers a new therapeutic target for aging interventions.

Keywords:
GSK-3Keap1NRF-2agingdietary restrictiontriglyceridesxenobiotic stress

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Area of Science:

  • Gerontology
  • Pharmacology
  • Molecular Biology

Background:

  • Extending healthspan through pharmacological interventions is a growing priority.
  • Identifying safe and effective compounds to promote longevity is crucial.

Purpose of the Study:

  • To investigate the potential of lithium, an FDA-approved drug, to promote longevity and healthspan.
  • To elucidate the molecular mechanisms underlying lithium's effects on aging.

Main Methods:

  • Administered lithium to adult female and male Drosophila throughout their lifespan or during later life stages.
  • Investigated the role of glycogen synthase kinase-3 (GSK-3) and nuclear factor erythroid 2-related factor (NRF-2) pathways.
  • Utilized genetic manipulation, including the loss of Kelch-like ECH-associated protein 1 (Keap1), to modulate NRF-2 activity.

Main Results:

  • Lithium administration significantly extended lifespan in both male and female Drosophila.
  • The pro-longevity effects of lithium were linked to the inhibition of GSK-3 and activation of NRF-2.
  • Combined lithium treatment with genetic NRF-2 activation demonstrated that high NRF-2 levels conferred stress resistance, while lower levels promoted longevity.

Conclusions:

  • Lithium effectively promotes longevity and healthspan, offering a potential therapeutic strategy for aging.
  • Inhibition of GSK-3 and modulation of NRF-2 are key mechanisms underlying lithium's anti-aging effects.
  • GSK-3 represents a promising therapeutic target for developing interventions to improve healthspan in mammals.