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Abstract：
Understanding the mechanisms of cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short lifespan and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. In this study, by analyzing experimental data it was shown that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional chemical-mechanical model was developed and used to suggest and test hypothesized mechanisms of bud morphogenesis during aging. Experimentally calibrated simulations showed that tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip guided by the polarized Cdc42 signal during the early stage of budding. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage, as observed in experiments, through a reduction on the new cell surface material insertion or an expansion of the polarization site. Thus model simulations suggest the maintenance of new cell surface material insertion or chemical signal polarization could be weakened due to cellular aging in yeast and other cell types.
摘要：
了解细胞衰老过程的机制对于试图延长生物体寿命和研究与年龄相关的退行性疾病至关重要。酵母细胞通过出芽分裂，为研究细胞衰老提供了经典的生物学模型。凭借他们强大的遗传学，在动物中也发现了相对较短的寿命和完善的信号通路，酵母细胞提供了对衰老过程的宝贵见解。最近的实验表明，酵母中存在两种衰老模式，其特征是核仁和线粒体下降，分别。在这项研究中,通过分析实验数据表明，进化成这两种衰老模式的细胞在年轻时表现不同。虽然芽在两种模式下线性生长，在整个生命周期中始终产生球形芽的细胞在年轻时控制芽的大小和生长速率方面表现出更大的功效。建立了三维化学力学模型，并用于建议和测试衰老过程中芽形态发生的假设机制。实验校准的模拟表明，在出芽的早期阶段，通过在极化的Cdc42信号的引导下在芽尖局部插入新材料，可以产生一种老化模式下的管状芽形状。此外，在后期可以稳定管状芽的长宽比，正如在实验中观察到的，通过减少新细胞表面材料的插入或极化位点的扩展。因此，模型模拟表明，由于酵母和其他细胞类型的细胞老化，新细胞表面材料插入或化学信号极化的维持可能会减弱。
■老化酵母表现出两种具有不同芽形状的模式。实验数据分析表明，在球形出芽模式下老化的细胞比在管状出芽模式下老化的细胞更可靠地控制生长速率和芽大小。开发了一个计算模型，并与实验结合使用，以测试衰老细胞中不同类型出芽的假设机制。模型模拟表明，局部生长足以产生管状出芽，并且可以通过调节极化位点扩大或新细胞表面材料插入下降的化学信号来稳定其纵横比。提出的衰老酵母形态变化的机制可以存在于其他细胞类型中。
■老化酵母表现出两种具有不同芽形状的模式。实验数据分析表明，在球形出芽模式下老化的细胞比在管状出芽模式下老化的细胞更可靠地控制生长速率和芽大小。开发了一个计算模型，并与实验结合使用，以测试衰老细胞中不同类型出芽的假设机制。模型模拟表明，局部生长足以产生管状出芽，并且可以通过调节极化位点扩大或新细胞表面材料插入下降的化学信号来稳定其纵横比。提出的衰老酵母形态变化的机制可以存在于其他细胞类型中。
