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Cited by 65Genetics, Aging, and Longevity in Model OrganismsAlzheimer's disease research and treatmentsFrailty in Older Adults

Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of Alzheimer’s Disease

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Kane, Alice E., Shin, Sooyoun, Wong, Aimee A., Fertan, Emre, Faustova, Natalia S., Howlett, Susan E., Brown, Richard E.·2018·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2018.00172PMC PMC6005856
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Abstract

Mouse models of Alzheimer's disease (AD) exhibit marked differences in life expectancy depending on their genotype and sex. The assessment of frailty could provide a measure of healthspan to facilitate comparisons between different AD models. We used a validated mouse frailty index (FI) assessment tool to explore genotype and sex differences in lifespan and healthspan of 3xTg-AD mice and their B6129F2 wild-type (WT) controls. This tool is based on an approach commonly used in people and quantifies frailty by counting the accumulation of age-related health deficits. The number of deficits in an individual divided by the total number measured yields an FI score theoretically between 0 and 1, with higher scores denoting more frailty. Male 3xTg-AD mice aged 300-600 days had higher FI scores (Mean FI = 0.21 ± 0.03) than either male WT (Mean FI = 0.15 ± 0.01) or female 3xTg-AD mice (Mean FI = 0.10 ± 0.01), and the elevated frailty scores were accompanied by parallel increases in mortality. Frailty increased exponentially with age, and higher rates of deficit accumulation elevated mortality risk in all groups of mice. When mice were stratified by FI score, frailty predicted mortality, at least in females. Therefore, the mouse clinical FI provides a valuable tool for evaluating healthspan in mouse models of AD with different lifespans.

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Cited by

Sorted by citations

Authors
Kane, A. E., Shin, S., Wong, A. A., Fertan, E., Faustova, N. S., Howlett, S. E., & Brown, R. E.
Affiliations
Dalhousie University (CA)
Corresponding author
Brown, Richard E.
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2018-06-12
Volume
10
Pages
172-172
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2018.00172
PMC
PMC6005856
OpenAlex
W2808078534
Cited by
65
References
9
Citations by year
2026: 5 · 2025: 4 · 2024: 14 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 10 · 2018: 1
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Natural Sciences and Engineering Research Council of Canada (RG 7441)
  • Canadian Institutes of Health Research (MOP 126018)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
Keywords
Alzheimer's disease, 3xTg-AD mice, sex differences, healthspan, lifespan, frailty, mortality, aging

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