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Abstract
The aging process is regarded as the progressive loss of physiological integrity, leading to impaired biological functions and the increased vulnerability to death. Among various biological functions, stress response capacity enables cells to alter gene expression patterns and survive when facing internal and external stresses. Here, we explored changes in stress response capacity during the replicative aging of Saccharomyces cerevisiae. To this end, we used a high-throughput microfluidic device to deliver intermittent pulses of osmotic stress and tracked the dynamic changes in the production of downstream stress-responsive proteins, in a large number of individual aging cells. Cells showed a gradual decline in stress response capacity of these osmotic-related downstream proteins during the aging process after the first 5 generations. Among the downstream stress-responsive genes and unrelated genes tested, the residual level of response capacity of Trehalose-6-Phosphate Synthase (TPS2) showed the best correlation with the cell remaining lifespan. By monitor dynamics of the upstream transcription factors and mRNA of Tps2, it was suggested that the decline in downstream stress response capacity was caused by the decline of translational rate of these proteins during aging.
Highlights
The aging process is regarded as the progressive loss of physiological integrity, leading to impaired biological functions and the increased vulnerability to death
The replicative lifespan (RLS) of budding yeast is examined in yeast aging studies; RLS is defined as the number of daughter cells produced by the mother cell before senescence[11]
The dynamics of the upstream transcription factors involved in the osmotic response and the mRNA of downstream protein were studied and found to be almost unchanged when face osmotic stress during cell aging, which suggested that the decline in downstream stress response capacity should caused by the decline of translational rate of these proteins during aging
Summary
The aging process is regarded as the progressive loss of physiological integrity, leading to impaired biological functions and the increased vulnerability to death. We explored changes in stress response capacity during the replicative aging of Saccharomyces cerevisiae To this end, we used a high-throughput microfluidic device to deliver intermittent pulses of osmotic stress and tracked the dynamic changes in the production of downstream stress-responsive proteins, in a large number of individual aging cells. Cells showed a gradual decline in stress response capacity of these osmotic-related downstream proteins during the aging process after the first 5 generations. Microfluidic devices allow for well-controlled microenvironments in studies investigating the biological processes of mother c ells[19] These devices can usually be combined with fluorescence microscopy to study the dynamics of important protein production during the cell aging process[20]. The dynamics of the upstream transcription factors involved in the osmotic response and the mRNA of downstream protein were studied and found to be almost unchanged when face osmotic stress during cell aging, which suggested that the decline in downstream stress response capacity should caused by the decline of translational rate of these proteins during aging
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