Carnitine promotes recovery from oxidative stress and extends lifespan in C. elegans

Aging (Albany NY). 2020 Dec 3;13(1):813-830. doi: 10.18632/aging.202187. Epub 2020 Dec 3.

Abstract

Carnitine is required for transporting fatty acids into the mitochondria for β-oxidation. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear. Here we show in C. elegans that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to H2O2 and human amyloid (Aβ) toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF-16. Long-lived worms with germline loss (glp-1) or reduced insulin receptor activity (daf-2) recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine. A new gene, T08B1.1, aligned to a known carnitine transporter OCTN1 in humans, is required for L-carnitine uptake in C. elegans. T08B1.1 expression is elevated in daf-2 and glp-1 mutants and its knockdown prevents L-carnitine from improving oxidative stress recovery and prolonging lifespan. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans.

Keywords: aging; amyloid; carnitine; oxidative stress; transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Amyloid beta-Peptides
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics*
  • Carnitine / pharmacology*
  • DNA-Binding Proteins / genetics*
  • Forkhead Transcription Factors / genetics*
  • Humans
  • Hydrogen Peroxide
  • Longevity / drug effects*
  • Naphthoquinones
  • Organic Cation Transport Proteins / genetics
  • Oxidative Stress / drug effects*
  • Paraquat
  • Reactive Oxygen Species / metabolism
  • Receptor, Insulin / genetics
  • Receptors, Notch / genetics
  • Stress, Physiological / drug effects*
  • Stress, Physiological / genetics
  • Transcription Factors / genetics*

Substances

  • Amyloid beta-Peptides
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Glp-1 protein, C elegans
  • Naphthoquinones
  • Organic Cation Transport Proteins
  • Reactive Oxygen Species
  • Receptors, Notch
  • Transcription Factors
  • daf-16 protein, C elegans
  • skn-1 protein, C elegans
  • Hydrogen Peroxide
  • DAF-2 protein, C elegans
  • Receptor, Insulin
  • Paraquat
  • Carnitine
  • juglone