On the robustness and response ability of aging-related gene regulatory network: Systems biology approach via microarray data

Aging, an extremely complex and system-level process, has attracted much attention in medical research, especially since chronic diseases are quite prevalent in the aged population. These may be the result of both gene mutations that lead to intrinsic perturbations and environmental changes that may stimulate signaling in the body. In addition, aging may result in diminished homeostasis and increased organism vulnerability, resulting in a reduced response to environmental stimuli such as carcinogens, oxidative stress and pro-inflammatory molecules. Therefore, measuring robustness to intrinsic perturbations and response ability to external stimuli of aging-related gene regulatory network may provide insight into the systematic mechanisms of aging. We show that an aging-related gene network is more robust to intrinsic perturbations in the elderly than the young, and therefore is less responsive to external stimuli i.e. there is a tradeoff between robustness and response ability in aging-related gene network in the aging process. These observations are consistent with experimental findings in phenotypes common in the aged population, for example tumorigenesis, pro-inflammation and declining resistance to oxidative stress. The methods described in this study may be used for future studies of gene regulatory networks involved in various biological processes and may have potential applications for gene therapy and drug target selection.