Probing polypharmacy, ageing and sex effects on physical function using different tests.
ageing
balance
endurance
grip strength
physical function
Journal
Fundamental & clinical pharmacology
ISSN: 1472-8206
Titre abrégé: Fundam Clin Pharmacol
Pays: England
ID NLM: 8710411
Informations de publication
Date de publication:
21 Jan 2024
21 Jan 2024
Historique:
revised:
01
12
2023
received:
24
06
2023
accepted:
14
12
2023
medline:
22
1
2024
pubmed:
22
1
2024
entrez:
22
1
2024
Statut:
aheadofprint
Résumé
Ageing, sex and polypharmacy affect physical function. This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups. Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10-6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6-8 weeks of treatment, mice were reassessed. High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance. Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.
Sections du résumé
BACKGROUND
BACKGROUND
Ageing, sex and polypharmacy affect physical function.
OBJECTIVES
OBJECTIVE
This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups.
METHODS
METHODS
Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10-6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6-8 weeks of treatment, mice were reassessed.
RESULTS
RESULTS
High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance.
CONCLUSION
CONCLUSIONS
Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : University of Sydney
Organisme : Penney Ageing Research Unit, Royal North Shore Hospital
Informations de copyright
© 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.
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