ArticleGeroScience2026
LINE-1 CpG methylation in canine blood and cortical DNA tracks epigenetic changes with age.
Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aging is accompanied by progressive epigenetic alterations, including changes in DNA methylation affecting both gene-associated regions and repetitive elements such as LINE-1 retrotransposons. Reduced epigenetic repression of transposable elements has been implicated in age-related genomic instability. Circulating cell-free DNA (cfDNA) provides a minimally invasive substrate for monitoring systemic molecular changes; however, age-related LINE-1 methylation dynamics in cfDNA remain poorly characterized in non-human species. Dogs represent a valuable translational model for aging research due to their shared environment with humans and shorter lifespan. We investigated age-associated LINE-1 CpG methylation in plasma-derived cfDNA and in prefrontal cortex genomic DNA from dogs. Sequence analysis of 264 potentially active canine LINE-1 elements identified a highly conserved central region spanning ORF1 and ORF2, with the targeted CpG site located within a locally low-variability segment, supporting multi-copy assessment. Methylation was quantified using methylation-sensitive restriction endonuclease digestion followed by real-time quantitative PCR (MSRED-PCR), with bisulfite conversion-based PCR (BSC-PCR) used for technical validation. In clinically healthy dogs, LINE-1 methylation in blood cfDNA showed a strong negative association with chronological age, best described by a nonlinear (logarithmic) model. In prefrontal cortex samples, older dogs exhibited significantly lower LINE-1 methylation compared to younger individuals. Across tissues, aging was consistently associated with LINE-1 hypomethylation. These findings indicate that age-related LINE-1 hypomethylation is detectable in both brain tissue and circulating cfDNA. While based on cross-sectional cohorts, the results suggest that LINE-1 methylation in cfDNA may represent a candidate minimally invasive marker of chronological aging in dogs.
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