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P-glycoprotein function in the elderly.

Stefanie S Brenner1, Ulrich Klotz

  • 1Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany.

European Journal of Clinical Pharmacology
|March 17, 2004
PubMed
Summary
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P-glycoprotein (Pgp) function, important for drug disposition, remains largely preserved in elderly individuals, with age and frailty showing minimal impact on its efflux activity in natural killer cells.

Area of Science:

  • Pharmacogenomics
  • Cellular Biology
  • Aging Research

Background:

  • P-glycoprotein (Pgp), encoded by the MDR1 gene, is a key efflux pump protecting against xenobiotics.
  • Genetic variations, including MDR1 single nucleotide polymorphisms (SNPs) like C3435T and G2677T/A, can influence Pgp expression and function.
  • The impact of aging and frailty on Pgp function has been largely unexplored.

Purpose of the Study:

  • To investigate age-dependent Pgp function in fit and frail elderly subjects.
  • To determine if Pgp efflux of rhodamine 123 from CD56(+) natural killer cells is affected by age, frailty, or specific MDR1 SNPs (C3435T and G2677T/A).

Main Methods:

  • Leukocytes were isolated from young healthy controls, fit elderly, and frail elderly individuals.
  • Subjects were genotyped for MDR1 SNPs C3435T (exon 26) and G2677T/A (exon 21).

Related Experiment Videos

  • Flow cytometry was used to measure rhodamine 123 efflux from CD56(+) cells.

    • Main Results:

    • No significant difference in rhodamine fluorescence was observed between CC and TT genotypes (C3435T) in elderly populations compared to young controls.
    • Frail elderly individuals with the TT genotype (C3435T) showed slightly reduced Pgp function (P=0.03) compared to young healthy subjects.
    • Overall, no significant age-related effects on Pgp function were detected when comparing groups independently of genotype, and no differences were found between fit and frail elderly subjects across all genotypes.

    Conclusions:

    • Aging and frailty appear to have a minimal impact on this cellular model of Pgp function.
    • Pgp function is likely well-preserved in individuals of advanced age, suggesting limited age-related alterations in this efflux mechanism.