報告題目：Systems Biology of cellular aging - Multigenerational silencing dynamics control cell aging

報  告 人🤽🏿‍♂️：Prof. Nan HAO (郝楠), University of California San Diego

報告時間：12月20日（周三）上午10:00

報告地點🖖：閔行校區生物藥學樓2號樓116會議室

聯  系 人👅：謝誌平 zxie@sjtu.edu.cn

報告摘要🚆：

Cellular aging plays an important role in many diseases, such as cancers, metabolic syndromes, and neurodegenerative disorders. There has been steady progress in identifying aging-related factors such as reactive oxygen species and genomic instability, yet an emerging challenge is to reconcile the contributions of these factors with the fact that genetically identical cells can age at significantly different rates. Such complexity requires single-cell analyses designed to unravel the interplay of aging dynamics and cell-to-cell variability. Here we use microfluidic technologies to track the replicative aging of single yeast cells and reveal that the temporal patterns of heterochromatin silencing loss regulate cellular life span. We found that cells show sporadic waves of silencing loss in the heterochromatic ribosomal DNA during the early phases of aging, followed by sustained loss of silencing preceding cell death. Isogenic cells have different lengths of the early intermittent silencing phase that largely determine their final life spans. Combining computational modeling and experimental approaches, we found that the intermittent silencing dynamics is important for longevity and is dependent on the conserved Sir2 deacetylase, whereas either sustained silencing or sustained loss of silencing shortens life span. These findings reveal that the temporal patterns of a key molecular process can directly influence cellular aging, and thus could provide guidance for the design of temporally controlled strategies to extend life span.

報告人簡介：

郝楠，博士。2001年於北京大學獲學士學位🪷，2006年於北卡羅來納大學獲博士學位，之後在北卡羅來納大學和哈佛大學/霍華德休斯研究所從事博士後研究🍬，2013年加入加州大學加州大學聖迭戈分校🥳。實驗室研究主要關註逆境🤌、衰老和疾病背景下的信號網絡結構及動態變化。