Abstract:
Why would a genotypically homogeneous population of cells live to different ages? We propose a mathematical model of cellular aging based on gene interaction network.  This model network is made of only non-aging components, and interactions among genes are inherently stochastic. Death of a cell occurs in the model when an essential gene loses all of its interactions. The key characteristic of aging, the exponential increase of mortality rate over time, can arise from this model network with non-aging components. Hence, cellular aging is an emergent property of this model network. The model predicts that the rate of aging, defined by the Gompertz coefficient, is proportional to the number of active interactions per gene and that stochastic heterogeneity is an important factor in shaping the dynamics of the aging process. Hence, the Gompertz parameter is a proxy of network robustness. Preliminary studies on how aging is influenced by power-law configuration, synthetic lethal interaction, and allelic interactions will be presented. A general framework to study network aging as a quantitative trait will be presented, and the implication on missing heritability will be discussed. Empirical results to support these theoretic studies will also be presented. Preprint for the basic model is available at http://arxiv.org/abs/1305.5784.

Collaborators:  Juhee Lee, UCSC; Yuan Ji and Kamalakar Gulukota, Northshore Hospital
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