Table 2.

Hallmarks of aging in lung cancer.

Feature	Effect	Reference
Genomic instability	The major cause of neoplasia, cancer initiation, progression, and impact the overall prognosis of the affected lung cancer patient	[41]
Inhibition of telomerase activity	Chromosome destabilization causes cellular senescence and death; in lung cancer telomere dysfunction promotes progression, metastasis and was associated with poor prognosis	[42,43]
Epigenetic mechanisms: (DNA hypermethylation, altered chromatin remodeling and histone modifications)	Established during differentiation, stably inherited and maintained through multiple rounds of cell division; deregulation of miRNAs is associated with early recurrence of lung cancer lesions	[42,44]
Mitochondrial DNA alteration	Plays a pivotal role in tumorigenesis; evasion of apoptosis	[42,45]
Intercellular communication	establishes a distinct tumor microenvironment (TME) with various stromal cell types to support growth, angiogenesis and invasion; altered communication of tumor cells to immune cells enable immune surveillance	[46]
Extracellular matrix (ECM) dysregulation	ECM actively undergoes dynamic remodeling during all stages of cancer progression; crosstalk between tumor cells and immune cells within primary and secondary sites is fundamental to ECM remodeling that feeds back to regulate tumor cell dormancy and outgrowth	[47]
Stem cell exhaustion	Cancer and aging are two possible endpoints of stem cells exposed to mutagenic hits, which will cause cell cycle arrest, and apoptosis or senescence. Through the acquisition of mutation and genetic or epigenetic alterations, normal stem cells can become CSCs	[48,49]