4.6 Article

The general law of plasma proteome alterations occurring in the lifetime of Chinese individuals reveals the importance of immunity

期刊

AGING-US
卷 14, 期 17, 页码 7065-7092

出版社

IMPACT JOURNALS LLC

关键词

lifespan; proteomics; biological processes; immune system; aging

资金

  1. National Key Research and Development Program of China [2018YFC2000400]
  2. Natural Science Foundation of China [81870552, 81400790, 81600622, 71490732, 91849118, 81849132, 81460203, 31760299, 81571385, 91849132, 81872096]
  3. Guangxi Natural Science Foundation [2014GXNSFDA118028, 2018GXNSFAA138156, guike0991198]
  4. Scientific Research Project of the health and family planning commission of Guangxi Zhuang Autonomous Region [Z20170162]
  5. Beijing Hospital Doctoral Scientific Research Foundation [BJ-2018-024]
  6. Beijing Hospital Nova Project [BJ-2018-139]
  7. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018RC330003]

向作者/读者索取更多资源

This study reveals the complex alterations in the plasma proteome over a human's lifetime, with the immune system playing a crucial role throughout the lifespan. However, the underlying mechanisms regulating differential protein expressions at different ages still need to be elucidated.
Background: Aging is characterized by a continuous loss of protein homeostasis. A closer examination of peripheral blood, which houses proteins from nearly all tissues and cells, helped identify several biomarkers and other aspects of aging biology. To further explore the general law of aging and identify key time nodes and associated aging biology, we collected 97 plasma samples from 253 healthy individuals aged 0-100 years without adverse outcomes to conduct nano-Ultra High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (nano-UHPLC-MS/MS) and weighted gene co-expression network analysis (WGCNA). Results: Through biological processes and key biological pathways identified in discrete age group modules, our analyses highlighted a strong correlation between alterations in the immune system and aging process. We also identified hub genes associated with distinct age groups that revealed alterations not only in protein expression but also in signaling cascade. Among them, hub genes from age groups of 0-20 years old and 71100 years old are mostly involved in infectious diseases and the immune system. In addition, CDC5L and HMGB2 were the key transcription factors (TFs) regulating genes expression in people aged between 51-60 and 71-100 years of age. They were shown to not only be independent but also mutually regulate certain hub gene expressions. Conclusions: This study reveals that the plasma proteome undergoes a complex alteration over the lifetime of a human. In this process, the immune system is crucial throughout the lifespan of a human being. However, the underlying mechanism(s) regulating differential protein expressions at distinct ages remains to be elucidated.

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