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