Maternal ancestry reveals cyclical aging of the mammary gland.

the present provocative data that in addition to the expected progressive age-related involution, mammary gland aging can occur in a cyclical pattern and is dictated by maternal ancestry. In cyclical aging, mammary glands of 11 and 19 months old mice share genetic and proteomic signatures, which are enriched in breast cancer-related pathways, but are absent at 3 and 14 months. Since incidence of breast cancer shows a bimodal age distribution at 45 (~11m in mice) and 65 (~19m in mice) in human populations, cyclical aging may contribute to these peaks of cancer susceptibility. Conversely, since the mammary glands at 3 and 14 months cluster together hierarchically, the cancer-associated peaks seem separated by a rejuvenation phase. Since cyclical aging is observed in mice with extended lifespan, these findings raise the possibility that if oncogenic mutations are avoided during the pro-oncogenic phases, through its rejuvenation phase, cyclical aging may impact multiple organs leading to extended longevity. We then performed single cells RNAseq analysis on primary mammary epithelium BL/6NZB females at 3M, 11M, 14M, and 19M of age