 Cells are not immortal.
 Cells can only undergo a limited number of cell division:
 usually about 50
 they then die
 It is not the type of death that is caused by damage or trauma, but an orderly series of events leading to cell death.
 This ordered or programmed cell death is called apoptosis.

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 During apoptosis:
 the cytoskeleton is broken down by enzymes
 the nuclear envelope and DNA fragment
 the cell membrane begins to bleb
 instead of invaginating as it does during phagocytosis, it forms little balloons that are pinched off from the cell surface membrane
 the blebs (vesicles) are phagocytosed

Apoptosis or programmed cell death
Normal cell, capable of dividing for a number of cycles – the Hayflick constant, about 50 divisions. After this, a series of ordered steps results in the death of the cell – not the same as necrosis!
Cell begins to break down. Enzymes digest the cytoskeleton and the cytoplasm becomes dense. The chromatin condenses and DNA fragments. Blebs (extrusions of the cytoplasm) appear containing cytoplasmic material.
Cell shrinks as it disintegrates. The blebs containing cytoplasm and organelles are phagocytosed (engulfed) by phagocytes and digested. Process is quick and prevents damage to surrounding tissues (if necrosis, enzymes and toxic products can cause extensive damage).
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 Apoptosis is controlled by a range of signalling molecules, e.g. cytokines, hormones and even chemicals like nitric oxide.
 It is part of normal development.
 Consider the changes that take place in the metamorphosis of amphibian:
 the larva (tadpoles) are aquatic, have external gills and a tail
 the adults have lungs, legs and no tail
 the gills and tail are reabsorbed due to apoptosis

Life cycle of amphibian.
The life cycle of an amphibian involves metamorphosis, with reabsorption of the gills and tail. Apoptosis is responsible for this.

 Similarly, during limb development in humans, the tissues have to be rearranged.
 Apoptosis allows for the separation of the digits
(fingers and toes).
 Failure of this leads to syndactyly, i.e. fused digits (toes in the case of the illustration opposite).
Failure of apoptosis leads to syndactyly or fused digits, as seen here on the foot.

Hand of newborn infant showing complete syndactyly of two fingers.
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 The balance between too much cell death and too little is important:
 too little and tissue accumulates
(tumour)
 too much and there is cell loss and tissue degeneration