Journal article
The reverse transcriptase inhibitor 3TC protects against age-related cognitive dysfunction
Aging cell, v 22(5), e13798
May 2023
PMID: 36949552
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aging is the primary risk factor for most neurodegenerative diseases, including Alzheimer's disease. Major hallmarks of brain aging include neuroinflammation/immune activation and reduced neuronal health/function. These processes contribute to cognitive dysfunction (a key risk factor for Alzheimer's disease), but their upstream causes are incompletely understood. Age-related increases in transposable element (TE) transcripts might contribute to reduced cognitive function with brain aging, as the reverse transcriptase inhibitor 3TC reduces inflammation in peripheral tissues and TE transcripts have been linked with tau pathology in Alzheimer's disease. However, the effects of 3TC on cognitive function with aging have not been investigated. Here, in support of a role for TE transcripts in brain aging/cognitive decline, we show that 3TC: (a) improves cognitive function and reduces neuroinflammation in old wild-type mice; (b) preserves neuronal health with aging in mice and Caenorhabditis elegans; and (c) enhances cognitive function in a mouse model of tauopathy. We also provide insight on potential underlying mechanisms, as well as evidence of translational relevance for these observations by showing that TE transcripts accumulate with brain aging in humans, and that these age-related increases intersect with those observed in Alzheimer's disease. Collectively, our results suggest that TE transcript accumulation during aging may contribute to cognitive decline and neurodegeneration, and that targeting these events with reverse transcriptase inhibitors like 3TC could be a viable therapeutic strategy.
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Details
- Title
- The reverse transcriptase inhibitor 3TC protects against age-related cognitive dysfunction
- Creators
- Devin Wahl - Colorado State UniversityMeghan E. Smith - Colorado State UniversityCali M. McEntee - Colorado State UniversityAlyssa N. Cavalier - Colorado State UniversityShelby C. Osburn - Colorado State UniversitySamuel D. Burke - Colorado State UniversityRandy A. Grant - Colorado State UniversityDavid Nerguizian - University of Colorado DenverDaniel S. Lark - Colorado State UniversityChristopher D. Link - University of Colorado BoulderThomas J. LaRocca - Colorado State University
- Publication Details
- Aging cell, v 22(5), e13798
- Publisher
- Wiley
- Number of pages
- 20
- Grant note
- AG060302; AG070562; AG078859; F32AG069361 / National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Health Sciences
- Web of Science ID
- WOS:000958271600001
- Scopus ID
- 2-s2.0-85150833783
- Other Identifier
- 991021894712604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Geriatrics & Gerontology