Aging is associated with a systemic length-associated transcriptome imbalance

Thomas Stoeger*, Rogan A. Grant, Alexandra C. McQuattie-Pimentel, Kishore R. Anekalla, Sophia S. Liu, Heliodoro Tejedor-Navarro, Benjamin D. Singer, Hiam Abdala-Valencia, Michael Schwake, Marie Pier Tetreault, Harris Perlman, William E. Balch, Navdeep S. Chandel, Karen M. Ridge, Jacob I. Sznajder, Richard I. Morimoto*, Alexander V. Misharin*, G. R.Scott Budinger*, Luis A. Nunes Amaral*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Aging is among the most important risk factors for morbidity and mortality. To contribute toward a molecular understanding of aging, we analyzed age-resolved transcriptomic data from multiple studies. Here, we show that transcript length alone explains most transcriptional changes observed with aging in mice and humans. We present three lines of evidence supporting the biological importance of the uncovered transcriptome imbalance. First, in vertebrates the length association primarily displays a lower relative abundance of long transcripts in aging. Second, eight antiaging interventions of the Interventions Testing Program of the National Institute on Aging can counter this length association. Third, we find that in humans and mice the genes with the longest transcripts enrich for genes reported to extend lifespan, whereas those with the shortest transcripts enrich for genes reported to shorten lifespan. Our study opens fundamental questions on aging and the organization of transcriptomes.

Original languageEnglish (US)
Pages (from-to)1191-1206
Number of pages16
JournalNature Aging
Volume2
Issue number12
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Aging
  • Neuroscience (miscellaneous)

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