Abstract 1311 Long Term Effect of Ashwagandha in Improving Brain Heath

Cells maintain their size to function in their ecological and organismal context.Most cells control their size by delaying cell cycle transitions until they reach a threshold cell size, suggesting that cells connect their growth and cell cycle signaling.Environmental factors influence the size of cells of both unicellular and multicellular organisms.The molecular mechanisms of how cells adapt their size to changing environments remains unclear.Fission yeast enter mitosis and divide at a threshold cell surface area due to size-dependent activation of Cyclin-dependent kinase (Cdk1).Recent work suggests this regulation is achieved by scaling the accumulation of mitotic activators with different aspects of cell size or growth.There is surface area-dependent accumulation of the protein kinase Cdr2, a Wee1 inhibitory kinase.Mitotic activator Cdc25 accumulates in the nucleus specifically with cell volume, while Cdc13 (Cyclin) nuclear concentration scales with cell cycle time.How cell surface area (Cdr2), time (Cyclin/ Cdc13), and cell volume-sensing (Cdc25) pathways contribute to cell size adaptation in low nutrient or stress conditions has been unknown.Using our high-throughput image analysis pipeline we measured the geometry of dividing cells grown under osmotic stress, oxidative stress, and low glucose conditions.We tested the importance of cell surface area, volume, or time-sensing pathways by modulating protein levels of Cdc25 (volume), Cdc13 (time), or Cdr2 (surface area).We depleted protein levels using degron-DaMP tagged Cdc25, Cdc13, or Cdr2 and doubled the expression of Cdr2, Cdc25, and Cdc13 by adding an additional copy of the gene at an exogenous locus.We find that wild type cells maximize their volume under oxidative stress but maximize their cell surface area under low glucose or osmotic stress.Interestingly, Cdc25 (volume) and Cdc13 (time) sensing pathways are necessary for cell size adaptation and cell volume increase under oxidative stress.The cell surface area (Cdr2) pathway was not required for cell size adaptation to osmotic stress or low nutrient conditions and maximized their cell surface area like wild type cells.These findings suggest that there may be back-up pathways for cell surface area sensing under these conditions.Our work identifies the role of size control pathways in cell adaptation to changing environments.