Aging, senescence, and cancer showed cell-type-specific transcriptional relationships, with senescence often opposing tumor-like programs.
Evidence
An integrative genomics, epigenomics, bulk transcriptomics, and single-cell transcriptomics analysis across 17 tissues identified 648 aging-dependent senescence-associated coregulated modules and opposing aging-cancer expression patterns in several cell types.
Caveat
The study infers biological relationships from computational multi-omic patterns rather than directly testing tumor formation or prevention in experimental systems.
Simplified
Cancer risk increases with age, and may be a major contributor to cellular carcinogenesis. Enormous efforts have been made to investigate the interrelation between aging and tumors, but little is known about the comparative features of normal aging, cellular senescence, and cancer at single-cell resolution. By integrating analyses of genomics, epigenomics, and bulk and single-cell transcriptomics, we revealed a directionally opposite transcriptional profile between cellular senescence and tumorigenesis at the single-cell level, which may be affected by epigenomic regulations. A total of 648 aging-dependent senescence-associated coregulated modules (SACMs), disproportionately affecting the reproductive systems of both females and males, were initially defined across 17 tissues. Single-cell analysis revealed that aging primarily affects endothelial cells, followed by T cells, epithelial cells, macrophages, and fibroblasts. Opposite directions of change in gene expression between aging and cancer can commonly be observed in endothelial, fibroblast, and epithelial cells, which may prompt the opposing patterns of gene expression between tissue aging and epithelial carcinoma at the bulk level. A similar pattern of expression can be observed in immune cells, which are characterized by decreased self-renewal with aging, but this pattern is reversed in epithelial carcinoma. Our study highlighted the role of senescence as a natural barrier against tumor formation and supported the idea that aging-related systemic environment changes create a protumorigenic milieu.
Key numbers
648
Identified
Total number of aging-dependent identified.
76% of 1217
Aging-Related Gene Changes
Percentage of cancer-suppressing genes significantly changing with aging.
86% of 397
Changes
Percentage of significantly changing with aging.
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