Abstract
Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Here, we characterize peripheral blood mononuclear cell transcriptome from 132 healthy adults with 21–90 years of age using the weighted gene correlation network analyses. In our study, 113 Caucasian from the 10KIP database and RNA-seq data of 19 Asian (Chinese) are used to explore the differential co-expression genes in PBMC aging. These two dataset reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1, and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Overall, the impact of age and race on transcriptional variation elucidated from this study may provide insights into the transcriptional driver of immune aging.
Highlights
Aging is a multifaceted process, involving numerous molecular and cellular mechanisms in the context of different organ systems (Lopez-Otin et al, 2013)
To identify main factors of variation in PBMC aging transcriptomic data, the microarray-based gene expression from 10 KIP provided by Lu et al (Zalocusky et al, 2018) was downloaded from the 10,000 immunomes project (10KIP, https://comphealth.ucsf.edu/app/10kimmunomes)
WGCNA is an integrated bioinformatic analyses, which is characterized effectively and systematically to find modules and gene signatures highly related with the clinical trait, and provides a comprehensive characterization of the transcriptomic changes for disease’s functional interpretation (Langfelder and Horvath, 2008)
Summary
Aging is a multifaceted process, involving numerous molecular and cellular mechanisms in the context of different organ systems (Lopez-Otin et al, 2013). A crucial component of aging is a set of functional and structural alterations in the immune system that can diminish the effectiveness of vaccinations, increase disease susceptibility, and contribute to mortality in older adults (NikolichZugich, 2018). In addition to alterations in the stromal microenvironment in primary and secondary lymphoid organs, cell-intrinsic changes like cell numbers, ratio, and function in both innate and adaptive immune cells play an important role in age-associated immune dysfunction. These alterations and transformations manifest themselves in increased morbidity and mortality of older organisms. The aim of this study is to exploit a large-scale population-based strategy to systematically identify genes and pathways differentially expressed as a function of chronological age
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