A deuterohemin peptide extends lifespan and increases stress resistance in Caenorhabditis elegans

Free Radic Res. 2010 Jul;44(7):813-20. doi: 10.3109/10715762.2010.485991.

Abstract

This group has invented a novel deuterohemin containing peptide deuterohemin-AlaHisThrValGluLys (DhHP-6), which has various biological activities including protection of murine ischemia reperfusion injury, improving cell survival and preventing apoptosis. It was hypothesized that DhHP-6 is beneficial on the lifespan of Caenorhabditis elegans (C. elegans) and increases their resistance to heat and oxidative stress. C. elegans were treated with different concentrations of DhHP-6. Survival time and sensitivity to heat and paraquat were investigated. The data demonstrated that the mean survival time of C. elegans was significantly increased (p < 0.05) in the DhHP-6 treated group compared with the control group. The maximum lifespan was not affected by DhHP-6 treatment. DhHP-6 improved the survival rate of C. elegans in the acute heat stress (35 degrees C) and rescued the C. elegans' sensitivity to paraquat in acute oxidative stress. Superoxide dismutase 3 (SOD-3) protein was up-regulated by DhHP-6 treatment. It was further demonstrated that stress resistance genes such as hsp-16.1, hsp-16.49 and sir-2.1 were regulated by DhHP-6. DAF-16 and SIR-2.1 genes are essential for the beneficial effect of DhHP-6. Therefore, the investigation into the beneficial effect of DhHP-6 on C. elegans' lifespan has the potential to develop novel drugs to prevent ageing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / drug effects*
  • Aging / genetics
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / biosynthesis
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology
  • Cytochromes b
  • Drug Evaluation, Preclinical
  • Forkhead Transcription Factors
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Genes, Helminth
  • Hemin / analogs & derivatives*
  • Hemin / pharmacology
  • Hot Temperature
  • Longevity / drug effects
  • Longevity / genetics
  • Oligopeptides / pharmacology*
  • Oxidative Stress / drug effects*
  • Paraquat / toxicity
  • Sirtuins / biosynthesis
  • Sirtuins / deficiency
  • Sirtuins / genetics
  • Sirtuins / physiology
  • Stress, Physiological / drug effects*
  • Succinate Dehydrogenase / deficiency
  • Succinate Dehydrogenase / physiology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • MEV-1 protein, C elegans
  • Oligopeptides
  • Transcription Factors
  • daf-16 protein, C elegans
  • deuterohemin-alanyl-histidyl-threonyl-valyl-glutamyl-lysine
  • Hemin
  • Cytochromes b
  • Succinate Dehydrogenase
  • SIR-2.1 protein, C elegans
  • Sirtuins
  • Paraquat