Cellular Death And Neurodegeneration

Question 0

Cellular senescence

Answer 0

Proteins and DNA accumulate damage

Changes in gene transcription

Question 1

Senescence

Answer 1

Deterioration of cellular function and the overall organism over time

Question 2

Organismal senescence

Answer 2

Summation of loss of cellular function

Increased chance of age associated disease

Question 3

2 types of aging

Answer 3

1. Chronological

2. Biological

Question 4

Chronological aging

Answer 4

Measured by the passing of time

Question 5

Biological aging

Answer 5

Difficult to measure
“Dog years”
How long you have had a car (chronological) v. How many miles it has (biological)

Question 6

Do all cells/organisms age?

Answer 6

Cancer cells never stop dividing–immortal
Hydra–regenerates from any portion of its body; cells are constantly dividing, removing old or damaged cells

Budding yeast–mother cell accumulates bud scars/damaged DN and proteins as they divide

Question 7

Sources of cellular damage

Answer 7

1. Environment
2. Metabolism
3. Infection

Question 8

Environment

Answer 8

Cells are damaged by chemical compounds that are ingested/inhaled
Destructive forms of radiation
Pollutants–air, water
UV radiation

Question 9

Reactive Oxygen Species

Answer 9

Extremely chemically reactive oxygen molecules
Oxygen molecule–unaired electrons; toxic to cell
Only 7 electrons in valence shell–will be highly reactive and make bonds/destroy existing bonds of other molecules in order to satisfy octet rule
Made in mitochondria
ROS damage proteins, DNA, lipids, etc
Cells deal with them using enzymes and antioxidants (proteins that can act as sensors)
Elevated in all major neurodegenerative diseases

Question 10

How do cells deal with damaged proteins and organelles?

Answer 10

Autophagy (“self-eating”)

Question 11

Autophagy

Answer 11

“Self-eating”
Digestion of unnecessary or disfunctional cellular components (misfolded proteins to full organelles)
When regulated, normal breakdown or material into its component parts
3 steps
Recycle
Protein-> amino acids
Misfolded proteins and amyloid fibers can be broken down through autophagy
Senescent cells have significantly reduced levels of autophagy–aggregates and lysosomes with material inside are not broken down; toxic to cell

Question 12

3 steps of autophagy

Answer 12

1. Isolate material in membrane bound vesicle
2. Fuse with the lysosome
3. Break down isolated material

Question 13

Programmed cellular death

Answer 13

Any self regulated induction of cellular death
Cell decides its own fate and induces its own destruction
Atrophic factors
Planned; does not only occur when something goes wrong

Question 14

Atrophic factors

Answer 14

Factors that force a cell to induce programmed cellular death

• decreased workload
• diminished blood supply
• inadequate nutrition
• loss of growth stimulation
• stimulated tissue morphologies

Question 15

Programmed cellular death pathways

Answer 15

Apoptosis--"self-destruction"
Cell's response to something bad (stress)
Heat
Radiation
Lack of nutrients/oxygen

Question 16

Neurodegeneration

Answer 16

Loss of neuronal structure and function
Post-mitotic–can’t remove cell damage through cell division
Size–long axons that are sensitive to damage

Question 17

Neurodegeneration in the brain

Central nervous system

Answer 17

Oligodendrocytes:

• die if not connected to active neurons
• do not clean extracellular space around healthy cells

Question 18

Neurodegeneration in the brain

Periphery nervous system

Answer 18

Schwann cells:

• aid in neuronal regrowth
• clear away myelin debris
• survive on their own

Question 19

Lifespan extension

Answer 19

Reduce oxidative damage–calorie restriction,”anti-aging” compounds in red wine (resveratrol)
Need autophagy