Apoptosis
Programmed cellular suicide that protects the body from cancer
Definition
Apoptosis is the main form of programmed cell death in multicellular organisms. Unlike necrosis (chaotic death with inflammation), apoptosis is an orderly and silent process: the cell condenses its chromatin, fragments its DNA, shrinks, and is phagocytised by macrophages before releasing pro-inflammatory content. It is essential for embryonic development, tissue turnover, and elimination of damaged or potentially tumoral cells.
Detailed explanation
Apoptosis is executed via two main pathways: the extrinsic pathway (mediated by death receptors such as Fas and TNF-R) and the intrinsic or mitochondrial pathway (regulated by the Bcl-2 protein family, with release of cytochrome c and activation of caspases). The balance between pro-apoptotic proteins (Bax, Bak) and anti-apoptotic proteins (Bcl-2, Bcl-xL) determines whether the cell lives or dies.
The p53 gene — known as 'the guardian of the genome' — is the main activator of apoptosis upon irreparable DNA damage. Its loss of function appears in 50% of human cancers.
With ageing, the regulation of apoptosis becomes unbalanced: damaged cells that should self-destruct instead enter senescence, accumulating and propagating the inflammatory SASP. Senolytics (dasatinib + quercetin, fisetin, navitoclax) aim to induce selective apoptosis in these resistant zombie cells to clear the aged tissue.
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