Cellular Senescence and Division

Types of Cells

Mitotic Cells

• Actively divide through mitosis
  • Examples: Epithelial cells (skin), fibroblast cells (scaffolding of organs), endothelial cells (lining of blood vessels)
  • Function: Replenish and regenerate tissues
  • Include stem cells

Post-Mitotic Cells

• Do not divide through mitosis
  • Examples: Neurons (brain/nervous system), heart muscle cells
  • Function: Limited ability to repair or regenerate tissues
  • **Utilize tissue-specific stem cells for slow regeneration

Mitosis and DNA Replication

• DNA Replication: Essential for creating new daughter cells
  • Linear DNA in eukaryotes
  • Telomeres: DNA caps that protect chromosome ends
  • DNA Polymerase: Does not copy DNA all the way to the ends
  • Telomere Shortening: Each replication cycle shortens telomeres
  • Replication Limit: 60-70 divisions before telomeres become critically short

Senescence

• Definition: A state where a cell loses its ability to divide
  • Triggered by: Shortened telomeres or DNA damage
  • Replicative Senescence: Due to telomere shortening
  • Hayflick Limit: Number of divisions before senescence (~60)
  • Changes in Senescent Cells: Gene expression, morphology, and responsiveness
  • Function: Prevent cancer/tumors by avoiding further DNA damage

Causes of Senescence

• Telomere malfunction
• DNA damage from: Mutations, toxins

Pros and Cons of Senescent Cells

• Pros: Prevent tumors/cancer
  • Cons: Reduced tissue repair, linked to age-related diseases like cataracts
  • Ongoing Research: Understanding the full impact

Post-Mitotic Cells and Senescence

• Do not replicate but can become senescent
  • Caused by: DNA damage or other threats

Division Capacity Graph

• Y-Axis: Cell division capacity
• X-Axis: Number of doublings (times a cell has divided)

Somatic Cells

• High initial capacity
  • Curve: Decreases with each division due to telomere shortening

Stem Cells

• High initial capacity
  • Curve: Remains high due to the enzyme Telomerase
  • Telomerase Function: Adds back lost telomeres during replication

Cancer Cells

• Can develop mutations expressing Telomerase
  • Outcome: Infinite replication, tumor formation