Meta‐analysis on blood transcriptomic studies identifies consistently coexpressed protein–protein interaction modules as robust markers of human aging

Abstract

The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein–protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10−38) enriched for ‘T-cell activation’ marking age-associated shifts in lymphocyte blood cell counts (R2 = 0.603; P = 1.9 × 10−10). Adjusting the analysis in the compendium for the ‘T-cell activation’ module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for ‘Translational elongation’, ‘Cytolysis’ and ‘DNA metabolic process’. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.

Identification of Potential Key lncRNAs and Genes Associated with Aging Based on Microarray Data of Adipocytes from Mice

“…In this study, Fbln1 and Fbln2 were discovered to be an age-regulated gene and regulated by the DE-lncRNA ENSMUSG00000086859 (gene name: 2810008D09Rik). The association of Fbln2 with human aging has also been discovered by previous studies [44, 45]. Moreover, Fbln5 was predicted to be targeted by ENSMUSG00000061510.…”

Inbred mouse strains reveal biomarkers that are pro‐longevity, antilongevity or role switching

“…This reflects the processes of ‘inflammaging’ (Franceschi et al ., 2006) and of ‘immunosenescence’ by involution of lymphocyte-producing thymic tissue, that is, the degeneration of the organ where these cells differentiate/mature (Domínguez-Gerpe & Rey-Méndez, 2003; Takahama, 2006; Chinn et al ., 2012). Consistent with this argument, a ‘T-cell activation’ module has been recently identified in humans, ‘marking age-associated shifts in lymphocyte blood cell counts’ (Van den Akker et al ., 2014). The increase of neutrophil numbers was also reported by others (Kovacs et al ., 2009), as was an age-dependent increase in granulocyte/macrophage progenitor cells (GMPs) (Rossi et al ., 2005).…”

How interacting pathways are regulated by miRNAs in breast cancer subtypes

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