On the Increase in Network Robustness and Decrease in Network Response Ability during the Aging Process: A Systems Biology Approach via Microarray Data

• Published in: IEEE/ACM transactions on computational biology and bioinformatics Vol. 10; no. 2; pp. 468 - 480
• Main Authors: Tu, Chien-Ta, Chen, Bor-Sen
• Format: Journal Article
• Language: English
• Published: United States IEEE 01.03.2013; The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
• Subjects: Aging; Aging - genetics; Caloric Restriction; Diseases; Forkhead Transcription Factors; Gene regulatory network; Gene Regulatory Networks; Genes; Genes, p53; Humans; Mice; network analysis; network response ability; network robustness; NF-kappa B - genetics; Older people; Oligonucleotide Array Sequence Analysis; Organ Specificity; Proteins - analysis; Proteins - genetics; Proteins - metabolism; Robustness; Stress; Systematics; systems biology; Systems Biology - methods
• DOI: 10.1109/TCBB.2013.23
• ISSN: 1545-5963; 1557-9964

Aging, an extremely complex and system-level process, has attracted much attention in medical research, especially since chronic diseases are quite prevalent in the elderly 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. Therefore, analysis of network robustness to tolerate intrinsic perturbations and network response ability of gene networks to respond to external stimuli during the aging process may provide insight into the systematic changes caused by aging. We first propose novel methods to estimate network robustness and measure network response ability of gene regulatory networks by using their corresponding microarray data in the aging process. Then, we find 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. Finally, we find that the response abilities of individual genes, especially FOXOs, NF-κB, and p53, are significantly different in the young versus the aged subjects. These observations are consistent with experimental findings in the aged population, e.g., elevated incidence of tumorigenesis and diminished resistance to oxidative stress. The proposed method can also be used for exploring and analyzing the dynamic properties of other biological processes via corresponding microarray data to provide useful information on clinical strategy and drug target selection.