Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer’s disease

INTRODUCTION: Declines in function occur in both normal aging (in the absence of disease) and age-related pathological contexts, like Alzheimers disease (AD). Whether anti-aging interventions (that extend lifespan) also promote cognitive function in aging and AD remains unexplored. METHODS: We assessed the effect of acarbose (1000 ppm from 4 months of age) on spatial learning and memory using the Morris water maze in young adult (6 mo), mid-aged (12 mo), or aged (24 mo) cohorts of normal aging (Ntg-HET3) and AD-relevant (5xFAD-HET3) genetically heterogeneous mice. RESULTS: In mid-aged and aged Ntg-HET3 mice, acarbose treatment resulted in performance equivalent to young adults. Conversely, acarbose failed to ameliorate age-related deficits in 5xFAD-HET3 mice. DISCUSSION: This work demonstrates that anti-aging interventions can also promote cognitive longevity in normal aging. Further, it reinforces that AD is not simply accelerated aging and requires therapies beyond anti-aging interventions that target its unique molecular and cellular drivers.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-05-01
DOI
https://doi.org/10.64898/2026.04.28.721469
Primary Topic
Genetics, Aging, and Longevity in Model Organisms
Type
article
Field-Weighted Citation Impact
0.00

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article

Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer’s disease

Shannon J. Moore, Geoffrey G. Murphy
bioRxiv (Cold Spring Harbor Laboratory)
Genetics, Aging, and Longevity in Model Organisms
article

Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer’s disease

Shannon J. Moore, Geoffrey G. Murphy
article en

Abstract

INTRODUCTION: Declines in function occur in both normal aging (in the absence of disease) and age-related pathological contexts, like Alzheimers disease (AD). Whether anti-aging interventions (that extend lifespan) also promote cognitive function in aging and AD remains unexplored. METHODS: We assessed the effect of acarbose (1000 ppm from 4 months of age) on spatial learning and memory using the Morris water maze in young adult (6 mo), mid-aged (12 mo), or aged (24 mo) cohorts of normal aging (Ntg-HET3) and AD-relevant (5xFAD-HET3) genetically heterogeneous mice. RESULTS: In mid-aged and aged Ntg-HET3 mice, acarbose treatment resulted in performance equivalent to young adults. Conversely, acarbose failed to ameliorate age-related deficits in 5xFAD-HET3 mice. DISCUSSION: This work demonstrates that anti-aging interventions can also promote cognitive longevity in normal aging. Further, it reinforces that AD is not simply accelerated aging and requires therapies beyond anti-aging interventions that target its unique molecular and cellular drivers.

bioRxiv (Cold Spring Harbor Laboratory)
University of Michigan (US), Laboratoire d’immunologie intégrative du cancer (FR), Neurology, Inc (US)
Glenn Foundation for Medical Research, National Institute on Aging
Openalex Percentile: Top 14%
Genetics, Aging, and Longevity in Model Organisms
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Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer’s disease — Shannon J. Moore, Geoffrey G. Murphy · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS