Senescent cell removal via JAG1-NOTCH1 signalling in the epidermis.
Level 5 - mechanism / opinion, no new human data
Mechanistic laboratory study using in vitro 3D reconstructed human epidermis models and human tissue samples.
PubMed 33891780 · doi:10.1111/exd.14361
What was done
Researchers examined Notch1 receptor expression in p16INK4a-positive senescent epidermal cells versus surrounding cells in tissue from young and old human subjects, alongside JAG1 ligand expression. They developed an in vitro 3D reconstructed human epidermis model mixing normal cells with UVB-irradiated senescent cells to track senescent cell localization, and tested the impact of JAG1 knockdown in normal cells or pharmacological Notch inhibition on cell clearance.
What was found
Notch1 receptor expression was higher in p16INK4a-positive senescent cells than adjacent cells in both young and old human epidermis, while JAG1 expression was decreased in aged epidermis. In the 3D skin model, UVB-induced senescent cells were selectively displaced from the basal layer to the upper epidermal layer. This basal clearance was inhibited either by JAG1 knockdown in surrounding normal cells or by Notch pathway inhibition. The abstract reports no quantitative values or effect sizes.
Why it matters
The study identifies a non-immune cell competition mechanism (JAG1-NOTCH1 signaling) responsible for purging senescent cells from the basal layer of the epidermis, suggesting that age-associated JAG1 downregulation may contribute to epidermal senescence accumulation.
Limits
The abstract provides no sample sizes (n), p-values, or quantitative measurements. Findings rely primarily on an artificial in vitro 3D culture system using UVB-induced senescence, which may not fully represent in vivo tissue dynamics or other forms of cellular senescence.
Cited by
- supports Cellular senescence occurs in the basal layer of keratinocytes in human skin.