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Inflammation promotes aging-associated oncogenesis in the lung
Catherine Pham-Danis1, Shi B Chia1, Hannah A Scarborough1
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Biorxiv : the Preprint Server for Biology
|March 18, 2024
Summary
Aging increases lung cancer risk by promoting inflammation. Studies show that targeting inflammation, like with alpha-1 antitrypsin (AAT), can reduce some aging-related lung changes and decrease tumor growth in older mice.
Area of Science:
- Oncology
- Immunology
- Gerontology
Background:
- Lung cancer is a leading cause of cancer death globally, with old age being a significant risk factor.
- Aging-associated chronic inflammation, or inflammaging, is implicated in increased lung cancer incidence, though the mechanisms are not fully understood.
Purpose of the Study:
- To investigate the connections between aging-associated lung changes and cancer risk.
- To elucidate the role of inflammaging in lung cancer development.
Main Methods:
- Analysis of gene expression databases (GTEx, TCGA) for normal and cancerous human lungs across age groups.
- Utilized mouse models to assess inflammation-dependent changes and their impact on oncogenesis.
- Investigated the effects of alpha-1 antitrypsin (AAT) and NLRP3 knockout on aging-related inflammation and lung cancer progression.
Main Results:
- Upregulated inflammatory pathways (e.g., TNFA signaling, interferon-gamma response) were identified in aging lungs and lung cancers.
- Transgenic alpha-1 antitrypsin (AAT) partially reversed aging-associated inflammation and immune deregulation markers.
- Old mice exhibited increased lung tumor outgrowth, which was reduced by NLRP3 knockout, indicating inflammation's role in aging-related lung cancer.
Conclusions:
- Aging contributes to increased lung cancer development, potentially via an enhanced inflammatory microenvironment.
- Mediators like AAT can mitigate some, but not all, aging-associated changes in lung gene and protein expression.
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