Integrative Omics Reveal Female-Specific Benefits of p16⁺ Cell Clearance in Aging Mice.

ABSTRACT: Aging is marked by the accumulation of cells expressing the cyclin-dependent kinase inhibitor p16Ink4a. These p16⁺ cells, largely senescent, contribute to inflammation and tissue dysfunction. While eliminating p16⁺ cells improves healthspan, sex-specific differences in their burden and clearance remain unclear. Through combined transcriptomic, proteomic, and functional analyses, we reveal distinct sex-dependent dynamics of p16⁺ cells during aging. Female mice accumulate significantly more p16⁺ cells across multiple tissues, particularly in the liver. In the p16-3MR model, selective ablation of these cells enhances grip strength, promotes skin regeneration, and reduces liver damage exclusively in females. Multi-omics profiling shows that p16⁺ cell removal shifts female liver expression towa

SUBMITTER: Lin Y 

PROVIDER: S-EPMC12806465 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature