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Screening candidate longevity therapeutics using gene-expression arrays.

Stephen R Spindler1, Patricia L Mote

  • 1Department of Biochemistry, University of California, Riverside, Calif 92521, USA. spindler@ucr.edu

Gerontology
|June 16, 2007
PubMed
Summary
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Caloric restriction (CR) extends lifespan and healthspan in mice, with effects linked to gene expression. Gene expression biomarkers may offer a superior method for screening longevity therapeutics compared to traditional lifespan studies.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Pharmacology

Background:

  • Caloric restriction (CR) rapidly extends healthspan and lifespan in mice, even in late adulthood.
  • Physiological effects of CR are linked to gene expression patterns in the liver and heart.
  • CR-associated longevity pathways may be relevant to human health and longevity.

Purpose of the Study:

  • To evaluate lifespan studies as an inefficient method for screening longevity therapeutics.
  • To explore gene expression patterns for identifying pharmaceuticals that mimic CR effects.
  • To identify novel longevity therapeutics.

Main Methods:

  • Traditional lifespan studies of various compounds (melatonin, pregnenolone, aminoguanidine, alpha-lipoic acid, coenzyme-Q10) in mice.

Related Experiment Videos

  • High-density microarray studies to assess drug-induced hepatic gene expression profiles.
  • Comparison of drug effects with gene-expression profiles from CR.

    • Main Results:

    • None of the tested compounds extended mouse lifespan in traditional studies.
    • Lifespan studies were time-consuming, expensive, and limited to identifying cancer chemopreventives.
    • Metformin was identified as a compound that mimics a subset of CR's gene-expression and physiological effects.

    Conclusions:

    • Gene-expression biomarkers are a more efficient and effective screening method for longevity therapeutics than lifespan studies.
    • This approach can accelerate the discovery of pharmaceuticals that promote healthspan and longevity.
    • Biomarker-driven screening holds promise for developing interventions for human aging.