Epithelial–mesenchymal transition to mitigate age-related progression in lung cancer.

Epithelial–Mesenchymal Transition (EMT) is a fundamental biological process involved in embryonic development, wound healing, and cancer progression. In lung cancer, EMT is a key regulator of invasion and metastasis, significantly contributing to the fatal progression of the disease. Age-related factors such as cellular senescence, chronic inflammation, and epigenetic alterations exacerbate EMT, accelerating lung cancer development in the elderly. This review describes the complex mechanism among EMT and age-related pathways, highlighting key regulators such as TGF-β, WNT/β-catenin, NOTCH, and Hedgehog signalling. We also discuss the mechanisms by which oxidative stress, mediated through pathways involving NRF2 and ROS, telomere attrition, regulated by telomerase activity and shelterin complex, and immune system dysregulation, driven by alterations in cytokine profiles and immune cell senescence, upregulate or downregulate EMT induction. Additionally, we highlighted pathways of transcription such as SNAIL, TWIST, ZEB, SIRT1, TP53, NF-κB, and miRNAs regulating these processes. Understanding these mechanisms, we highlight potential therapeutic interventions targeting these critical molecules and pathways. [Display omitted] • EMT plays crucial role in invasion and metastasis, contributing significantly to the progression of lung cancer. • Senescence, chronic inflammation, and epigenetic shifts in aging accelerate EMT, promoting lung cancer progression. • Key signaling regulators such as TGF-β, Wnt/β-catenin, Notch, and Hedgehog are highlighted for their roles in EMT initiation and progression. • NRF2 and ROS contribute to oxidative stress and telomere shortening, regulated by telomerase and shelterin, driving EMT progression. • Transcription factors and molecules like Snail, Twist, Zeb, SIRT1, p53, NF-κB, and miRNAs are highlighted as EMT pathway regulators. [ABSTRACT FROM AUTHOR]