Age-Associated Inflammation Connects RAS-Induced Senescence to Stem Cell Dysfunction and Epidermal Malignancy

The study demonstrated that mutant H-Ras activation in mouse epidermis led to different outcomes based on age, with young mice showing hyperplasia and rapid hair growth, while aged mice exhibited more dysplasia and progression to in situ squamous cell carcinoma (SCC). This progression in aged mice was linked to increased inflammation, immune cell accumulation, and cell senescence. There was also an age-dependent increase in pro-inflammatory mediators, anti-inflammatory responses, and expression of the immune suppressive ligand Pdl1. Additionally, aged skin failed to regenerate after switching off H-Ras activity, indicating a dysfunction in aged epidermal stem cells. These findings suggested that the accumulation of senescent cells and immune infiltration in aged skin contributed to higher cancer risk in older individuals.