Spurious intragenic transcription is a feature of mammalian cellular senescence and tissue aging

Payel Sen, Greg Donahue, Catherine Li, Gabor Egervari, Na Yang, Yemin Lan, Neil Robertson, Parisha P. Shah, Erik Kerkhoven, David C. Schultz, Peter D. Adams, Shelley L. Berger

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Mammalian aging is characterized by the progressive loss of tissue function and increased risk for disease. Accumulation of senescent cells in aging tissues partly contributes to this decline, and targeted depletion of senescent cells in vivo ameliorates many age-related phenotypes. The fundamental molecular mechanisms responsible for the decline of cellular health and fitness during senescence and aging are largely unknown. In this study, we investigated whether chromatin-mediated loss of transcriptional fidelity, known to contribute to fitness and survival in yeast and worms, also occurs during human cellular senescence and mouse aging. Our findings reveal aberrant transcription initiation inside genes during senescence and aging that co-occurs with changes in the chromatin landscape. Interventions that alter these spurious transcripts have profound consequences on cellular health, primarily affecting intracellular signal transduction pathways. We propose that age-related spurious transcription promotes a noisy transcriptome and degradation of coherent transcriptional networks.

Original languageEnglish
Pages (from-to)402-417
Number of pages16
JournalNature Aging
Volume3
Issue number4
DOIs
StatePublished - Apr 2023

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