Age-associated changes in transcriptional elongation and their effects on homeostasis.
Abstract
Cellular homeostasis declines with age due to the declining fidelity of biosynthetic processes and the accumulation of molecular damage. Yet, it remains largely elusive how individual processes are affected during aging and what their specific contribution to age-related functional decline is. This review discusses a series of recent publications that has shown that transcription elongation is compromised during aging due to increasing DNA damage, stalling of RNA polymerase II (RNAPII), erroneous transcription initiation in gene bodies, and accelerated RNAPII elongation. Importantly, several of these perturbations likely arise from changes in chromatin organization with age. Thus, taken together, this work establishes a network of interlinked processes contributing to age-related decline in the quantity and quality of RNA production.
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Research summary
The paper discusses the mechanisms of transcriptional elongation and its decline with age, which is pertinent to understanding the biological processes underlying aging. It highlights how these changes contribute to age-related functional decline, thus addressing root causes of aging rather than merely treating symptoms. However, while the findings are solid and contribute to the field, they do not present groundbreaking insights that would significantly alter current understanding or approaches to longevity research.
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