| Summary: | Summary: Single-cell-level experimentation can elucidate key biological insights about cellular aging that are masked in population-level studies. However, the extensive time requirement of tracking single cells has historically prevented their long-term longitudinal observation. Using a microfluidic device that automates microscopic monitoring of diploid Saccharomyces cerevisiae cells throughout their replicative lifespan, here we report the fundamental characteristics of single-cell aging for diploid yeast. We find that proteins with short versus long half-lives exhibit distinct dynamics as cells age and that the intercellular gene expression noise increases during aging, whereas the intracellular noise stays unchanged. A stochastic model provides quantitative mechanistic insights into the observed noise dynamics and sheds light on the age-dependent intracellular noise differences between diploid and haploid yeast. Our work elucidates how a set of canonical phenotypes dynamically change while the host cells are aging in real time, providing essential insights for a comprehensive understanding on and control of lifespan at the single-cell level. : Gene Network; Systems Biology; Biological Science Instrumentation Subject Areas: Gene Network, Systems Biology, Biological Science Instrumentation
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