Cell Aging and Death

Necrosis

  • Necrosis: death of tissues
    • No energy required
    • Always pathological

Coagulative necrosis

  • Preservation of cell outline
  • Microenvironment too toxic for proteolysis – cells can’t clear up mess
  • Common, often seen in MI

Liquefactive necrosis

  • No cell structure remains
  • Viscous mass of dead cells left behind - pus
  • Bacterial + fungal infections, brain injury

Caseous necrosis

  • ‘Cheesy’
  • TB

Apoptosis

  • Apoptosis: programmed cell death in response to specific signals
  • Requires energy
  • May be either physiological (normal growth, removal of self-reactive lymphocytes, hormonal-dependent involution) or pathological (injury, chemo, viral infection)

Pathways for apoptosis

Extrinsic
  • Initiated by death receptors which activate caspases
  • Fas: recognition of self
    • Apoptosis in lymphocytes
    • Fas mutations → autoimmune diseases
  • TNF: apoptosis in association with inflammation
Intrinsic
  • Mitochondrial pathway
  • Growth signals promote anti-apoptotic molecules in mitochondrial membrane - replaced by Bax + Bak when removed which stimulate caspase release

p53

  • Senses damage to DNA, can halt cell cycle
  • If DNA can’t be repaired, stimulates caspases

Cellular aging

  • Many causes
    • Oxidative stress - free radical damage
    • Accumulation of metabolic by-products - lipofuscin
  • Calorie restriction can extend life - reduces IGF signaling which can silence specific genes