Aging atlas reveals cell-type-specific effects of pro-longevity strategies

Nat Aging. 2024 Jul;4(7):998-1013. doi: 10.1038/s43587-024-00631-1. Epub 2024 May 30.

Abstract

Organismal aging involves functional declines in both somatic and reproductive tissues. Multiple strategies have been discovered to extend lifespan across species. However, how age-related molecular changes differ among various tissues and how those lifespan-extending strategies slow tissue aging in distinct manners remain unclear. Here we generated the transcriptomic Cell Atlas of Worm Aging (CAWA, http://mengwanglab.org/atlas ) of wild-type and long-lived strains. We discovered cell-specific, age-related molecular and functional signatures across all somatic and germ cell types. We developed transcriptomic aging clocks for different tissues and quantitatively determined how three different pro-longevity strategies slow tissue aging distinctively. Furthermore, through genome-wide profiling of alternative polyadenylation (APA) events in different tissues, we discovered cell-type-specific APA changes during aging and revealed how these changes are differentially affected by the pro-longevity strategies. Together, this study offers fundamental molecular insights into both somatic and reproductive aging and provides a valuable resource for in-depth understanding of the diversity of pro-longevity mechanisms.

MeSH terms

  • Aging* / genetics
  • Aging* / physiology
  • Animals
  • Caenorhabditis elegans* / genetics
  • Gene Expression Profiling
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Longevity* / genetics
  • Organ Specificity
  • Polyadenylation / genetics
  • Transcriptome*