Targeted partial reprogramming of age-associated cell states improves markers of health in mouse models of aging

The study aims to explore the effects of CDKN2A-OSK expression across various tissues and human primary cells using next-generation sequencing. Mouse tissues and human cultured cells were collected at specific time points, followed by RNA extraction and next-generation sequencing. The sequencing data for mouse RNA were aligned to the mm9 genome, while the human RNA data were aligned to the Hg38 genome using standard RNA alignment and analysis protocols. LAKI mice were transduced with AAV carrying Cdkn2a-OSK (also referred as p16-OSK) on day 60, and tissues were harvested on day 135 for downstream RNA processing. IMR90 cells were serially passaged to different culture ages, representing various stages of senescence. IMR90 cells undergoing stress-induced aging were generated by treatment with various stressors, including DNA-damaging agents like etoposide and bleomycin, and oncogenic RAS. AAV-DJ was added at the specified culture ages, with media replenished every other day. Cells were analyzed 12 days post-AAV treatment. Day 20 cells represent healthy cells, day 125 cells represent late senescence, and days 50 and 85 represent intermediate stages.