Germain Doris, Mashaka Thelma, Chattopadhyay Mrittika, Polushakov Dmitry, Torres-Martin Miguel, Sia Daniela, Jenkins Edmund
Icahn School of Medicine at Mount Sinai.
Barcelona Institute of Science and Technology.
Res Sq. 2024 Nov 21:rs.3.rs-4926839. doi: 10.21203/rs.3.rs-4926839/v1.
We 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), 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.
我们展示了具有启发性的数据，即除了预期的与年龄相关的渐进性退化外，乳腺衰老可能以周期性模式发生，并且由母系血统决定。在周期性衰老中，11个月和19个月大的小鼠乳腺具有共同的基因和蛋白质组特征，这些特征在与乳腺癌相关的途径中富集，但在3个月和14个月时不存在。由于乳腺癌发病率在45岁（小鼠约11个月）和65岁（小鼠约19个月）呈现双峰年龄分布，周期性衰老可能导致这些癌症易感性高峰。相反，由于3个月和14个月的乳腺在层次上聚集在一起，与癌症相关的高峰似乎被一个年轻化阶段隔开。由于在寿命延长的小鼠中观察到周期性衰老，这些发现提出了一种可能性，即如果在致癌前期避免致癌突变，通过其年轻化阶段，周期性衰老可能影响多个器官，从而延长寿命。
