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Once hypoxia is established in the tissue microenvironment, cellular HIF-1 is not hydroxylated and therefore forms a heterodimer with HIF-1 initiating a cellular adaptive program by inducing the transcription of genes such as vascular endothelial growth factor A ( VEGFA ), TGFB , insulin-like growth factor 2 ( IGF2 ), collagen type 2 alpha 1 ( COL2A1 ), and aggrecan ( ACAN )

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Over time, this cumulative oxidative stress impairs mitochondrial function, disrupts cell signaling, and promotes inflammation - all hallmarks of biological aging