Biology subjects

McCormick, M. A.

Publications and source records attributed to McCormick, M. A..

2 recordsLinked to original sources

bioRxiv2020

Single-cell RNA-seq reveals early heterogeneity during ageing in yeast

The budding yeast Saccharomyces cerevisiae has relatively short lifespan and is genetically tractable, making it a widely used model organism in ageing research. Here, we carried out a systematic and quantitative investigation of yeast ageing with single-cell resolution through transcriptomic sequencing. We optimized a single-cell RNA sequencing (scRNA-seq) protocol to quantitatively study the whole transcriptome profiles of single yeast cells at different ages, finding increased cell-to-cell transcriptional variability during ageing. The single-cell transcriptome analysis also highlighted key biological processes or cellular components, including oxidation-reduction process, oxidative stress response (OSR), translation, ribosome biogenesis and mitochondrion that underlie ageing in yeast. Remarkably, we uncovered a molecular marker, FIT3, that was linked to mitochondrial DNA loss and indicated the early heterogeneity during ageing in yeast. We also analyzed the regulation of transcription factors and further characterized the distinctive temporal regulation of the OSR by YAP1 and proteasome activity by RPN4 during ageing in yeast. Overall, our data profoundly reveal early heterogeneity during ageing in yeast and shed light on the ageing dynamics at the single cell level.

genomics↗

bioRxiv2018

Translation Attenuation by Minocycline Increases Lifespan and Improves Proteostasis in Old Post-Stress-Responsive Organisms

Aging impairs the activation of Stress Signaling Pathways (SSPs), preventing the induction of longevity mechanisms late in life. Here we show that the antibiotic minocycline increases lifespan and reduces protein aggregation even in old, SSP-deficient C. elegans by targeting cytoplasmic ribosomes, preferentially attenuating translation of highly translated mRNAs. In contrast to most other longevity paradigms, minocycline inhibits rather than activates all major SSPs and extends lifespan in mutants deficient in the activation of SSPs, lysosomal or autophagic pathways. We propose that minocycline lowers the concentration of newly synthesized aggregation-prone proteins, resulting in a relative increase in protein-folding capacity without the necessity to induce protein-folding pathways. Our study suggests that in old individuals with incapacitated SSPs or autophagic pathways, pharmacological attenuation of cytoplasmic translation is a promising strategy to reduce protein aggregation. Altogether, it provides a geroprotecive mechanism for the many beneficial effects of tetracyclines in models of neurodegenerative disease.

physiology↗