Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model

Michael Bene1, Adam B Salmon2,3,4

  • 1Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA.

Geroscience
|January 13, 2023
PubMed

Insights

Longevity interventions in worms (C. elegans) and flies (Drosophila) show limited success in predicting lifespan extension in mice. This suggests caution when translating findings across species for human aging research.

Area of Science:

  • Gerontology and aging research
  • Comparative biology
  • Pharmacology and drug discovery

Background:

  • Numerous compounds extend lifespan in model organisms like Caenorhabditis elegans, Drosophila, and mice.
  • The conservation of these pro-longevity effects across different species remains largely unknown.
  • Understanding cross-species translational potential is crucial for developing effective human aging interventions.

Purpose of the Study:

  • To evaluate the extent to which longevity interventions in Caenorhabditis and Drosophila predict lifespan extension in mice.
  • To assess the translatability of pro-longevity findings from invertebrate models to mammalian systems.
  • To inform the development of reliable biomarkers and models for aging research.

Main Methods:

  • Analysis of published longevity intervention studies from the DrugAge database.
  • Focus on reproducible results from the National Institute on Aging (NIA)-supported Interventions Testing Program (ITP) and Caenorhabditis Interventions Testing Program (CITP).
  • Comparative analysis of compound effects on lifespan across C. elegans, Drosophila, and mouse models.

Main Results:

  • Drosophila interventional studies demonstrated only modest sensitivity and specificity in predicting pro-longevity compounds in mouse lifespan studies.
  • Surprisingly, C. elegans studies showed minimal predictive value for identifying drugs that extend lifespan in mice.
  • Significant discrepancies were observed in the cross-species efficacy of tested longevity interventions.

Conclusions:

  • Findings suggest limited translatability of lifespan-extending compounds identified in C. elegans and Drosophila to mouse models.
  • Caution is advised when extrapolating longevity intervention results across species, including implications for human aging.
  • Further research is needed to identify reliable cross-species biomarkers and predictive models for aging interventions.