Evidence map›Paper›PMID 33780539›Full record

ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021

Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions.

Harry Wu, John Mach, Gizem Gemikonakli, Trang Tran, Heather Allore, Danijela Gnjidic, Susan E Howlett, Rafael de Cabo, David G Le Couteur, Sarah N Hilmer

Open access · greenAbstract read
In one paragraph

Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 26 citations in OpenAlex.

  1. Frailty, polypharmacy, deprescribing, and 23-hour activity: insights from a mouse model.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Polypharmacy and precision medicine.Cambridge prisms. Precision medicine · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Harry WuDepartments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
John MachLaboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney and Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Gizem GemikonakliLaboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney and Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Trang TranLaboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney and Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Heather AlloreDepartment of Internal Medicine, Yale University, New Haven, Connecticut, USA.ORCID 0000-0001-7685-8175
Danijela GnjidicSydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Susan E HowlettDepartments of Pharmacology and Medicine (Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada.ORCID 0000-0001-5351-6308
Rafael de CaboTranslational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.ORCID 0000-0003-2830-5693
David G Le CouteurCharles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-4227-5817
Sarah N HilmerDepartments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, New South Wales, Australia.ORCID 0000-0002-5970-1501
The University of Sydney · AUDalhousie University · CANational Institutes of Health · USYale University · US

Funding

Yale Study Support Suite (YES3): Dashboard and Web Portal Software Supporting Research Workflow through integrated, customizable REDCap External ModulesP30AG021342 · NIA · YALE UNIVERSITY · PI Albert C Shaw · 2002 to 2026
$37.9M
Individualized Absolute Risk calculator For Persons With Multiple Chronic ConditionsR01AG047891 · NIA · YALE UNIVERSITY · PI ALLORE, HEATHER GWYNN · 2015 to 2017
$990k
NIA NIH HHS P30 AG021342NIH HHS R01 AG047891
6 · The paper itself

Abstract

Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6-8/group) for 4-6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p < .001). Old animals had a greater decline in nesting score (p < .05) and midzone distance (p < .001) than young animals. Grip strength declined more in males than females (p < .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes.

Indexed as

Pharmaceutical PreparationsPolypharmacyActivities of Daily LivingAnimalsFemaleHumansMaleMiceMice, Inbred C57BLWalking SpeedPharmaceutical PreparationsDrug burden indexGeriatric pharmacologyPolypharmacySex

Identifiers

PMID33780539
PMCPMC8436985
OpenAlexW3143417644

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.