Systems-level analysis of human aging genes shed new light on mechanisms of aging

Quanwei Zhang, Ruben Nogales-Cadenas, Jhih Rong Lin, Wen Zhang, Ying Cai, Jan Vijg, Zhengdong Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although studies over the last decades have firmly connected a number of genes and molecular pathways to aging, the aging process as a whole still remains poorly understood. To gain novel insights into the mechanisms underlying aging, instead of considering aging genes individually, we studied their characteristics at the systems level in the context of biological networks. We calculated a comprehensive set of network characteristics for human aging-related genes from the GenAge database. By comparing them with other functional groups of genes, we identified a robust group of aging-specific network characteristics. To find the structural basis and the molecular mechanisms underlying this aging-related network specificity, we also analyzed protein domain interactions and gene expression patterns across different tissues. Our study revealed that aging genes not only tend to be network hubs, playing important roles in communication among different functional modules or pathways, but also are more likely to physically interact and be co-expressed with essential genes. The high expression of aging genes across a large number of tissue types also points to a high level of connectivity among aging genes. Unexpectedly, contrary to the depletion of interactions among hub genes in biological networks, we observed close interactions among aging hubs, which renders the aging subnetworks vulnerable to random attacks and thus may contribute to the aging process. Comparison across species reveals the evolution process of the aging subnetwork. As the organisms become more complex, the complexity of its aging mechanisms increases and their aging hub genes are more functionally connected.

Original languageEnglish (US)
Pages (from-to)2934-2947
Number of pages14
JournalHuman Molecular Genetics
Volume25
Issue number14
DOIs
StatePublished - 2016

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Genes
Protein Interaction Domains and Motifs
Gene Expression
Essential Genes
Communication
Databases

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Systems-level analysis of human aging genes shed new light on mechanisms of aging. / Zhang, Quanwei; Nogales-Cadenas, Ruben; Lin, Jhih Rong; Zhang, Wen; Cai, Ying; Vijg, Jan; Zhang, Zhengdong.

In: Human Molecular Genetics, Vol. 25, No. 14, 2016, p. 2934-2947.

Research output: Contribution to journalArticle

Zhang, Quanwei ; Nogales-Cadenas, Ruben ; Lin, Jhih Rong ; Zhang, Wen ; Cai, Ying ; Vijg, Jan ; Zhang, Zhengdong. / Systems-level analysis of human aging genes shed new light on mechanisms of aging. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 14. pp. 2934-2947.
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