Transposable element small and long RNAs in aging brains and implications in Huntington's and Parkinson's disease
Abstract
Transposable Elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact of brain TE RNA dynamics on these phenomena is not fully understood. Therefore, we quantified TE RNA changes in aging post-mortem human and mouse brains and in the neurodegenerative disorders Huntingtons Disease (HD) and Parkinsons Disease (PD). We tracked TE small RNAs (smRNAs) expression landscape to assess the relationship to the active processing from TE long RNAs (lnRNAs). Human brain transcriptomes from the BrainSpan Atlas displayed a significant shift of TE smRNA patterns at age 20 years, whereas aging mouse brains lacked any such marked change, despite clear shift in aging-associated mRNA levels. Human frontal cortex displayed pronounced sense TE smRNAs during aging with a negative relationship between the TE smRNAs and lnRNAs indicative of age associated regulatory effects. Our analysis revealed TE smRNAs dysregulation in HD, while PD showed a stronger impact on TE lnRNAs, potentially correlating with the early average age of death for HD relative to PD. Furthermore, TE-silencing factor TRIM28 was down-regulated only in aging human brains, possibly explaining the lack of substantial TE RNA changes in aging mouse brains. Our study suggests brain TE RNAs may serve as novel biomarkers of human brain aging and neurodegenerative disorders.
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Research summary
The paper investigates the role of transposable elements (TEs) and their RNA dynamics in aging and neurodegenerative diseases, specifically Huntington's and Parkinson's disease. This focus on the molecular mechanisms underlying aging processes and their implications for age-related diseases aligns with longevity research. However, while the findings contribute to our understanding of TE RNA dynamics in the context of aging, the impact appears to be solid but limited, as it primarily provides insights rather than groundbreaking solutions to the root causes of aging.
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