Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

Interactome networks and human disease

The role of DNA damage and repair in aging through the prism of Koch-like criteria

Hundreds of genes and miRNAs have been identified as being involved in the determination of longevity, aging patterns and in the development of age-related diseases (ARDs). The interplay between these genes as well as the role of miRNAs in the context of protein-protein interaction networks has as yet been poorly addressed. This work was undertaken in order to integrate the data accumulated in the field, from a network-based perspective. The results are organized in the NetAge database-an online database and network analysis tools for biogerontological research ( http://www.netage-project.org ). The NetAge database contains gene sets and miRNA-regulated PPI networks for longevity, ARDs and aging-associated processes, and also common signatures (overlapping networks). The database is available through the NetAge website, which provides the necessary bioinformatics tools for searching and browsing the networks, as well as showing network info and statistics. By making these resources available online, we hope to provide the scientific community with a new, network-oriented platform for biogerontological research, and encourage greater participation in the systems biology of aging.

The NetAge database: a compendium of networks for longevity, age-related diseases and associated processes.

http://www.pnei-it.com/1/upload/hormesis_and_epigenetic_prew.pdf

Hormesis and epigenetics: is there a link?

Aging of the cells: Insight into cellular senescence and detection Methods

Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

/pdf/a-multidimensional-systems-biology-analysis-of-cellular-2mskpotel0.pdf

A multidimensional systems biology analysis of cellular senescence in aging and disease

Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses. We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases. By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes. Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

/pdf/a-multidimensional-systems-biology-analysis-of-cellular-626d0t1agr.pdf

Arie Budovsky

Papers

A multidimensional systems biology analysis of cellular senescence in aging and disease

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

MicroRNAs: Relevance to Aging and Age-Related Diseases