Age is the greatest risk factor for breast cancer. Yet, the accumulation of mutations with age alone is insufficient to explain the age-dependent increase in breast-cancer incidence. The process of aging is associated with gradual breast-tissue changes that are accompanied by epigentic, transcriptional, and post-transcriptional changes. However, it remains unclear how these age-related molecular and cellular changes contribute to breast-cancer development. We hypothesize that changes in RNA-splicing regulation during aging could contribute to pre-neoplastic state and prime the mammary gland for cancer development. With the support of the Jackson Aging Center, we are proposing to carry out preliminary experiments aimed at ultimately identifying genes and cell types associated with age-related changes in RNA-splicing regulation that take place in the murine mammary gland and are likely to contribute to brast cancer development.