CELL SENESCENCE & PROGRAMMED CELL DEATH<br />DR. JAYAKARA BHANDARY M.<br />SENIOR SCALE LECTURER IN BOTANY<br />GOVERNMENT...
Cell Senescence<br />Deteriorative process  which naturally  slows  down  and terminates the functional  life of a cell.<b...
	Cell  senescence          Organismal   	senescence            Death.
Cells and Organisms are not immortal.</li></li></ul><li>Senescence indicated by..<br /><ul><li>Decline in functional effic...
Cellular changes during senescence<br />Morphological :<br /><ul><li>Change in  cell size and shape – Atrophy
Accumulation of Lipofuscin pigment.
Nuclear pyknosis.
Lipid vacuole formation.	</li></li></ul><li>Cellular changes during senescence<br />2. Physiological changes:<br /><ul><li...
   Loss of ribosomal RNA.
   Decline in transcription .
   Decline in protein synthesis.
   Stiffening of collagen .
   Decline in  energy production.</li></li></ul><li>Cellular changes during senescence<br />3. Sub-cellular changes:<br />...
 	Decrease in granular ER.
 	Degeneration of mitochondria.
 	Degeneration of chloroplasts (plant  	cells).</li></li></ul><li>Young Fibroblast cells<br />
Senescent fibroblast cells<br />
Theories of Senescence<br /><ul><li> 	Molecular Mechanism not clearly 	and completely  understood.
 	Studied  mainly in animal cells.
 	Many theories.</li></li></ul><li>1. DNA Damage theories<br />	Accumulated damage to DNA inhibits cell functions and divi...
 	Damage to mitochondrial DNA – 	Decrease in energy production .</li></li></ul><li>2. Built-in Breakdown theories (Genetic...
 	Formation of DNA synthesis 	inhibiting proteins.</li></li></ul><li>3. Telomere Theory<br />Gradual shortening of Telomer...
Replicative cell senescence.</li></li></ul><li>Telomere shortening during cell divisions<br />
4. Free radical damage theory<br />Damage by highly reactive free radicals like OH, O2, H2O2 , etc.<br /><ul><li>	Disrupts...
	Alters membrane permeability.
	Damage DNA / Proteins.
Antioxidants reduce free radical  	damage.</li></li></ul><li>Other Theories…<br /><ul><li>Glycation theory – Glucose forms...
Immune theory – Antibodies against 	body’s own cells – autoimmune 	responses.
Endocrine theory – A  pitutary 	hormone triggers senescence.</li></li></ul><li>Importance  of understanding senescence…<br...
 	Understanding  formation of cancerous  	cells -  Failure of senescence 	mechanism?
 	Cure for cancer by promoting 	senescence?</li></li></ul><li>
Programmed Cell Death (PCD) or Apoptosis<br />Cells committing suicide by 	the activation of an intra-	cellular death prog...
 	A neat, silent  death of cells.</li></li></ul><li>Apoptosis<br /><ul><li> 	No damage to neighboring  cells, 	as 	in Necr...
 	Different from autophagy- intracellular 	digestion by acid hydrolases of 	Lysosomes.</li></li></ul><li>
Apoptosis<br /><ul><li> 	Mainly mediated by a group of </li></ul>proteolytic enzymes called  Caspaces.<br /><ul><li>Presen...
Activated to kill cells by death 	signals.
The Poison Pills of Cells!</li></li></ul><li>Mechanism of PCD<br /><ul><li> 	Reception of  death or apoptotic 	signals 	(I...
 	Activation of Inactive Procaspasesto 	active  Caspases (Cascade Reaction)</li></li></ul><li>Mechanism of PCD..<br /><ul>...
 	Fragmentation  of  DNA/Nucleus.
 	Shrinkage and blebbing of cells.</li></li></ul><li>Mechanism of PCD – contd.<br /><ul><li> 	Formation of smaller membran...
 	Digestion of apoptotic bodies by  	macrophages – Phagocytosis.
 	Recycling  of the macro-molecules.</li></li></ul><li>
A  normal  cell<br />
A normal cell<br />An apoptotic cell<br />
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Cell senescence and Apoptosis (PCD)

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Molecular mechanisms and biological functions of Cell senescence and Apoptosis or PCD.

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Cell senescence and Apoptosis (PCD)

  1. 1. CELL SENESCENCE & PROGRAMMED CELL DEATH<br />DR. JAYAKARA BHANDARY M.<br />SENIOR SCALE LECTURER IN BOTANY<br />GOVERNMENT ARTS AND SCIENCE COLLEGE<br />KARWAR -581301, KARNATAKA, INDIA<br />jaikarb@yahoo.com<br />PRESENTED IN:<br />EDUSAT BASED TRAINING PROGRAM FOR PU TEACHERS OF KARNATAKA<br />DEPARTMENT OF PRE-UNIVERSITY EDUCATION, GOVT. OF KARNATAKA<br />2008<br />
  2. 2. Cell Senescence<br />Deteriorative process which naturally slows down and terminates the functional life of a cell.<br /><ul><li> Cell Aging process.
  3. 3. Cell senescence Organismal senescence Death.
  4. 4. Cells and Organisms are not immortal.</li></li></ul><li>Senescence indicated by..<br /><ul><li>Decline in functional efficiency of </li></ul>specialised non-dividing cells.<br />Eg: Nerve cells, muscle cells.<br /><ul><li>Decline of division capacity of actively dividing cells (Replicative senescence / Heyflick effect).</li></ul>Eg: Lymphocytes, Epithelial cells.<br />
  5. 5. Cellular changes during senescence<br />Morphological :<br /><ul><li>Change in cell size and shape – Atrophy
  6. 6. Accumulation of Lipofuscin pigment.
  7. 7. Nuclear pyknosis.
  8. 8. Lipid vacuole formation. </li></li></ul><li>Cellular changes during senescence<br />2. Physiological changes:<br /><ul><li> Accumulation of calcium ions.
  9. 9. Loss of ribosomal RNA.
  10. 10. Decline in transcription .
  11. 11. Decline in protein synthesis.
  12. 12. Stiffening of collagen .
  13. 13. Decline in energy production.</li></li></ul><li>Cellular changes during senescence<br />3. Sub-cellular changes:<br /><ul><li> Change in fluidity and permeability of plasma membrane.
  14. 14. Decrease in granular ER.
  15. 15. Degeneration of mitochondria.
  16. 16. Degeneration of chloroplasts (plant cells).</li></li></ul><li>Young Fibroblast cells<br />
  17. 17. Senescent fibroblast cells<br />
  18. 18. Theories of Senescence<br /><ul><li> Molecular Mechanism not clearly and completely understood.
  19. 19. Studied mainly in animal cells.
  20. 20. Many theories.</li></li></ul><li>1. DNA Damage theories<br /> Accumulated damage to DNA inhibits cell functions and division.<br /><ul><li>Decline in DNA repair capacity – Gene expression inhibited.
  21. 21. Damage to mitochondrial DNA – Decrease in energy production .</li></li></ul><li>2. Built-in Breakdown theories (Genetic theories)<br />Genetically programmed process. Senescence associated genes express after a fixed life span of cells.<br /><ul><li> Expression of genes coding for hydrolytic enzymes.
  22. 22. Formation of DNA synthesis inhibiting proteins.</li></li></ul><li>3. Telomere Theory<br />Gradual shortening of Telomeres with each division / Reduction in telomerase activity. <br /><ul><li>Division stops when telomere becomes very short.
  23. 23. Replicative cell senescence.</li></li></ul><li>Telomere shortening during cell divisions<br />
  24. 24. 4. Free radical damage theory<br />Damage by highly reactive free radicals like OH, O2, H2O2 , etc.<br /><ul><li> Disrupts cell and nuclear membranes.
  25. 25. Alters membrane permeability.
  26. 26. Damage DNA / Proteins.
  27. 27. Antioxidants reduce free radical damage.</li></li></ul><li>Other Theories…<br /><ul><li>Glycation theory – Glucose forms cross-links between proteins and stiffens them.
  28. 28. Immune theory – Antibodies against body’s own cells – autoimmune responses.
  29. 29. Endocrine theory – A pitutary hormone triggers senescence.</li></li></ul><li>Importance of understanding senescence…<br /><ul><li> Extending life-span of cells & organisms by delaying senescence.
  30. 30. Understanding formation of cancerous cells - Failure of senescence mechanism?
  31. 31. Cure for cancer by promoting senescence?</li></li></ul><li>
  32. 32. Programmed Cell Death (PCD) or Apoptosis<br />Cells committing suicide by the activation of an intra- cellular death program.<br /><ul><li> Apoptosis (APP-oh-TOE-sis, John Kerr et al. 1972) means Falling Off, like the leaves of a tree in autumn.
  33. 33. A neat, silent death of cells.</li></li></ul><li>Apoptosis<br /><ul><li> No damage to neighboring cells, as in Necrosis-Cell death by swelling and exploding due to injury or damage.
  34. 34. Different from autophagy- intracellular digestion by acid hydrolases of Lysosomes.</li></li></ul><li>
  35. 35. Apoptosis<br /><ul><li> Mainly mediated by a group of </li></ul>proteolytic enzymes called Caspaces.<br /><ul><li>Present in all cells in an inactive form calledProcaspaces.
  36. 36. Activated to kill cells by death signals.
  37. 37. The Poison Pills of Cells!</li></li></ul><li>Mechanism of PCD<br /><ul><li> Reception of death or apoptotic signals (Internal / external).
  38. 38. Activation of Inactive Procaspasesto active Caspases (Cascade Reaction)</li></li></ul><li>Mechanism of PCD..<br /><ul><li> Degradation of cytoplasmic and nuclear proteins.
  39. 39. Fragmentation of DNA/Nucleus.
  40. 40. Shrinkage and blebbing of cells.</li></li></ul><li>Mechanism of PCD – contd.<br /><ul><li> Formation of smaller membrane bound structures called apoptotic bodies.
  41. 41. Digestion of apoptotic bodies by macrophages – Phagocytosis.
  42. 42. Recycling of the macro-molecules.</li></li></ul><li>
  43. 43. A normal cell<br />
  44. 44.
  45. 45.
  46. 46.
  47. 47. A normal cell<br />An apoptotic cell<br />
  48. 48. Procaspase activation<br />
  49. 49. Caspase activation cascade<br />
  50. 50.
  51. 51.
  52. 52. Significance of PCD <br />Normal process during development. Responsible for sculpturing of body parts during development of animals.<br /><ul><li>Development of animal paws.
  53. 53. Metamorphosis of tadpole into Frog, insect larva into pupa. </li></li></ul><li>Apoptosis during paw development<br />
  54. 54. Cells of the tadpole tail undergo apoptosis during metamorphosis into a frog<br />
  55. 55. 131 of 1090 cells undergo apoptosis in Coenorhabditiselegans (Nematode).<br />
  56. 56. Significance of PCD …<br />Balancing number of cells in developing Tissues (homeostasis).<br /><ul><li> Adjusting the number of nerve cells to match the number of target cells.
  57. 57. About 85% of certain nerve cell populations die during development of vertebrate nervous system. Ex. Dorsal root sensory ganglia of Chick embryo.</li></li></ul><li>
  58. 58. Significance of PCD …<br /> Eliminating unwanted / improperly formed / functionless / dangerous cells.<br /><ul><li> Virus infected cells, cancer cells, improperly developed thymocytes, activated lymphocytes, etc.</li></li></ul><li>Apoptosis in Plant cells<br /><ul><li> Degradation of Nucleus
  59. 59. Disappearance of cytoplasm
  60. 60. Packaging inside small vacuoles </li></li></ul><li>Apoptosis in Plant cells<br /><ul><li> Differentiation of xylem tracheary elements.
  61. 61. Destroying pathogen infected cells.
  62. 62. During plant development.</li></li></ul><li>Differentiation of vessel element by apoptosis<br />Nucleus and cytoplasm degraded by apoptosis<br />
  63. 63. Cells of wheat seedling undergoing apoptosis<br />Apoptotic vacuoles with cellular debris<br />
  64. 64. Applications of understanding apoptosis<br /><ul><li> Killing cancer cells by activating PCD?.
  65. 65. Certain auto-immune diseases are due to failure of apoptosis in cells which should die.
  66. 66. Apoptosis in cells which should not die leads to abnormal development / disorders (Neuro - degenerative problems). </li></li></ul><li>T H A N K Y O U<br />

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