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Background: SPRY1 is associated with the invasiveness and prognosis of various tumors, and TET3 affects aging by regulating gene expression. Aims: We investigated the roles of SPRY1 and TET3 in natural skin aging, replicative aging, and photoaging, along with the effect of UVA on genome‐wide DNA methylation in HaCaT cells. Methods: TET3 and SPRY1 expression were measured in the skin of patients of different age groups, as well as in vitro human skin, HaCaT cell replicative senescence, and HaCaT and HaCaT‐siTET3 cell photoaging models. Senescence was verified using β‐galactosidase staining, and DNA damage was detected using immunofluorescence staining for γ‐H2A.X. 5‐Methyl cytosine (5‐mC) content in the genome was determined using ELISA. Results: SPRY1 expression increased with age, whereas TET3 expression decreased. Similarly, SPRY1 was upregulated and TET3 was downregulated with increasing cell passages. TET3‐siRNA upregulated SPRY1 expression in HaCaT cells. UVA irradiation promoted HaCaT cell senescence and induced cellular DNA damage. SPRY1 was upregulated and TET3 was downregulated upon UVA irradiation. Genome‐wide 5‐mC content increased upon TET3 silencing and UVA irradiation, indicating a surge in overall methylation. Conclusions: SPRY1 and TET3 are natural skin aging‐related genes that counteract to regulate replicative aging and UVA‐induced photoaging in HaCaT cells. The cell photoaging model may limit experimental bias caused by different exposure times of skin model samples. [ABSTRACT FROM AUTHOR]

The article discusses a study on single-cell DNA methylation and 3D genome architecture in the human brain. The research provides a comprehensive atlas of epigenomic characteristics, revealing cell-type specificity, chromatin structures, and DNA methylation patterns, which will be valuable for understanding brain cell diversity, gene regulation mechanisms, and the development of genetic tools.