Postmitotic cell longevity–associated genes: a transcriptional signature of postmitotic maintenance in neural tissues

Atahualpa Castillo-Morales, Jimena Monzón-Sandoval, Araxi O. Urrutia, Humberto Gutiérrez

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4 Citations (SciVal)

Abstract

Different cell types have different postmitotic maintenance requirements. Nerve cells, however, are unique in this respect as they need to survive and preserve their functional complexity for the entire lifetime of the organism, and failure at any level of their supporting mechanisms leads to a wide range of neurodegenerative conditions. Whether these differences across tissues arise from the activation of distinct cell type–specific maintenance mechanisms or the differential activation of a common molecular repertoire is not known. To identify the transcriptional signature of postmitotic cellular longevity (PMCL), we compared whole-genome transcriptome data from human tissues ranging in longevity from 120 days to over 70 years and found a set of 81 genes whose expression levels are closely associated with increased cell longevity. Using expression data from 10 independent sources, we found that these genes are more highly coexpressed in longer-living tissues and are enriched in specific biological processes and transcription factor targets compared with randomly selected gene samples. Crucially, we found that PMCL-associated genes are downregulated in the cerebral cortex and substantia nigra of patients with Alzheimer's and Parkinson's disease, respectively, as well as Hutchinson-Gilford progeria-derived fibroblasts, and that this downregulation is specifically linked to their underlying association with cellular longevity. Moreover, we found that sexually dimorphic brain expression of PMCL-associated genes reflects sexual differences in lifespan in humans and macaques. Taken together, our results suggest that PMCL-associated genes are part of a generalized machinery of postmitotic maintenance and functional stability in both neural and non-neural cells and support the notion of a common molecular repertoire differentially engaged in different cell types with different survival requirements.

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalNeurobiology of Aging
Volume74
Early online date19 Oct 2018
DOIs
Publication statusPublished - 1 Feb 2019

Funding

The authors thank Leticia Ramirez-Lugo from the National University of Mexico for her technical support. This work was funded by CONACyT PhD scholarships to AC-M and JM-S, a Royal Society Dorothy Hodgkin Research Fellowship (grant number DH071902 ), Royal Society research grant (grant number RG0870644 ) and a Royal Society research grant for fellows (grant number RG080272 ) to AOU as well as Institutional funding from the University of Lincoln to HG. Authors' contributions: AOU and HG conceived and designed the study. AC-M and JM-S carried out the analyses presented. All authors contributed to the preparation of the manuscript. Appendix A

Keywords

  • Cell longevity
  • Functional genomics
  • Neural maintenance
  • Transcriptional signature

ASJC Scopus subject areas

  • General Neuroscience
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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