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<p>Aging is a complex and systematic biological process that involves multiple genes and biological pathways across different tissues. While existing studies focus on tissue-specific aging factors, the inter-tissue interplay between molecular pathways during aging remains insufficiently explored. To bridge this gap, we propose a novel computational framework to identify the effect of aging on the coordinated patterns of gene-expression across multiple tissues. Our framework includes (1) an adjusted multi-tissue weighted gene co-expression network analysis, (2) differential network connectivity analysis between age groups and (3) machine learning models, XGBoost and Random Forest (RF) fed by gene expression levels and lower-dimensional pathway score space, to identify unique key inter-tissue genes and biological pathways for classifying aging. We applied our approach to three representative tissues: Adipose-Subcutaneous, Muscle-Skeletal and Brain-Cortex. The RF model demonstrated the best performance in predicting age group (AUC &lt; 88%) highlighting key genes involved in inter-tissue coordination processes in aging. We also identified the inter-tissue involvement of lipid metabolism, immune system, and cell communication pathways during aging and detected distinct aging pathways manifested between tissues. The proposed framework highlights the importance of inter-tissue coordination processes underlying aging and provides valuable insights into aging mechanisms which can further assist in the development of therapeutic strategies promoting healthy aging.</p>

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A computational framework for detecting inter-tissue gene-expression coordination changes with aging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月31日

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  • Shaked Briller,
  • Gil Ben David,
  • Yam Amir,
  • Gil Atzmon,
  • Judith Somekh

摘要

Aging is a complex and systematic biological process that involves multiple genes and biological pathways across different tissues. While existing studies focus on tissue-specific aging factors, the inter-tissue interplay between molecular pathways during aging remains insufficiently explored. To bridge this gap, we propose a novel computational framework to identify the effect of aging on the coordinated patterns of gene-expression across multiple tissues. Our framework includes (1) an adjusted multi-tissue weighted gene co-expression network analysis, (2) differential network connectivity analysis between age groups and (3) machine learning models, XGBoost and Random Forest (RF) fed by gene expression levels and lower-dimensional pathway score space, to identify unique key inter-tissue genes and biological pathways for classifying aging. We applied our approach to three representative tissues: Adipose-Subcutaneous, Muscle-Skeletal and Brain-Cortex. The RF model demonstrated the best performance in predicting age group (AUC < 88%) highlighting key genes involved in inter-tissue coordination processes in aging. We also identified the inter-tissue involvement of lipid metabolism, immune system, and cell communication pathways during aging and detected distinct aging pathways manifested between tissues. The proposed framework highlights the importance of inter-tissue coordination processes underlying aging and provides valuable insights into aging mechanisms which can further assist in the development of therapeutic strategies promoting healthy aging.