CELL SENESCENCE & PROGRAMMED CELL DEATH

DR. JAYAKARA BHANDARY M.SENIOR SCALE LECTURER IN BOTANY

GOVERNMENT ARTS AND SCIENCE COLLEGEKARWAR -581301, KARNATAKA, INDIA

jaikarb@yahoo.com

PRESENTED IN:EDUSAT BASED TRAINING PROGRAM FOR PU TEACHERS OF KARNATAKADEPARTMENT OF PRE-UNIVERSITY EDUCATION, GOVT. OF KARNATAKA

2008

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.

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.

Cellular changes during senescence

1. Morphological :

Change in cell size and shape – Atrophy Accumulation of Lipofuscin pigment. Nuclear pyknosis. Lipid vacuole formation.

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.

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).

Young Fibroblast cells

Senescent fibroblast cells

Theories of Senescence

Molecular Mechanism not clearly and completely understood.

Studied mainly in animal cells.

Many theories.

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 .

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.

3. Telomere Theory Gradual shortening of Telomeres with

each division / Reduction in telomerase activity.

Division stops when telomere becomes very short.

Replicative cell senescence.

Telomere shortening during cell divisions

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.

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.

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?

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.

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.

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!

Mechanism of PCD

Reception of death or apoptotic signals (Internal / external).

Activation of Inactive Procaspases to active Caspases (Cascade Reaction)

Mechanism of PCD..

Degradation of cytoplasmic and nuclear proteins.

Fragmentation of DNA/Nucleus.

Shrinkage and blebbing of cells.

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.

A normal cell

A normal cell An apoptotic cell

Procaspase activation

Caspase activation cascade

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.

Apoptosis during paw development

Cells of the tadpole tail undergo apoptosis during metamorphosis into a frog

131 of 1090 cells undergo apoptosis in Coenorhabditis elegans (Nematode).

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.

Significance of PCD …Eliminating unwanted / improperly formed / functionless / dangerous cells.

Virus infected cells, cancer cells, improperly developed thymocytes, activated lymphocytes, etc.

Apoptosis in Plant cells Degradation of Nucleus

Disappearance of cytoplasm

Packaging inside small vacuoles

Apoptosis in Plant cells Differentiation of xylem

tracheary elements.

Destroying pathogen infected cells.

During plant development.

Differentiation of vessel element by apoptosis

Nucleus and cytoplasm degraded by apoptosis

Cells of wheat seedling undergoing apoptosis

Apoptotic vacuoles with cellular debris

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).

T H A N K Y O U