工程延长寿命——设计合成基因振荡器以减缓细胞衰老。
Engineering longevity-design of a synthetic gene oscillator to slow cellular aging.
机构信息
Department of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA.
Synthetic Biology Institute, University of California San Diego, La Jolla, CA 92093, USA.
出版信息
Science. 2023 Apr 28;380(6643):376-381. doi: 10.1126/science.add7631. Epub 2023 Apr 27.
Abstract
Synthetic biology enables the design of gene networks to confer specific biological functions, yet it remains a challenge to rationally engineer a biological trait as complex as longevity. A naturally occurring toggle switch underlies fate decisions toward either nucleolar or mitochondrial decline during the aging of yeast cells. We rewired this endogenous toggle to engineer an autonomous genetic clock that generates sustained oscillations between the nucleolar and mitochondrial aging processes in individual cells. These oscillations increased cellular life span through the delay of the commitment to aging that resulted from either the loss of chromatin silencing or the depletion of heme. Our results establish a connection between gene network architecture and cellular longevity that could lead to rationally designed gene circuits that slow aging.
摘要
合成生物学使基因网络的设计能够赋予特定的生物学功能，但要合理设计出像寿命这样复杂的生物学特性仍然是一个挑战。一种自然发生的切换开关是酵母细胞衰老过程中核仁或线粒体衰退的命运决定的基础。我们重新布线了这个内源性的切换开关，设计了一个自主的遗传时钟，在单个细胞的核仁与线粒体衰老过程之间产生持续的振荡。这些振荡通过延迟由于染色质沉默丧失或血红素耗竭而导致的衰老承诺，从而延长了细胞寿命。我们的结果在基因网络结构和细胞寿命之间建立了联系，这可能导致设计出能够减缓衰老的合理基因电路。
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