Stanford University

Analysis of Gene Expression of Aging in C. elegans

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This proposal aims to discover the molecular mechanism of cell degeneration associated with aging by examining the age-dependent change of activity of a large number of genes. Gene activity in a cell can be visualized by image of Green Fluorescence Protein (GFP) reporter. However, descriptive image can not be directly used by computational analysis to subtract information from a large amount of data. So the first specific aim of this proposal is to develop an image analysis algorithm to automatically identify cells in a worm and assign gene activity to every cell.

Like other animals, C. elegans exhibit different types of deterioration in different tissues in the course of aging. Fluorescent microscopy shows that pigmented granules accumulate in gut of aged worms, and electron microscopy shows that old worms exhibit morphological degeneration of their muscle and intestinal cells but not neural tissue. The second specific aim of this proposal is to discover the mechanism of tissue-specific aging.

In addition to the variance between tissues, aging shows the seemingly random nature of large variations even between individual cells of same tissue. The stochastic deterioration suggests a “catastrophic noise” model of aging. Gene activity may be tightly regulated in young animals so that cells can function efficiently. However, gene regulation becomes noisy in old animals and leads to functional degeneration associated with age. The third specific aim of this proposal is to test this “catastrophic noise” model of aging by measuring the variance of gene activity between individual cells.