Block 3 Lecture 2 -- Cell Death Flashcards
What are the 2 categories of aging theories?
1) biologically programmed
2) Accumulation of Errors / Damage
What is the programmed senescence theory?
genetics regulate program
- Hayflicks limits
- Telomerase theory
- based on salmon spawning producing massing steroid release leading to death
What is Hayflicks limits?
fibroblasts die after 50 divisions
What are the biologically programmed theories?
1) programmed senescence
2) immune senescence
3) endocrine senescence
What is the endocrine senescence theory?
decreased HP-ovarian fx leads to sexual senescence and hormone decreases, along with less responsive organs
– more difficult to maintain homeostasis
What is the immune senescence theory?
change in immune system leads to infection disease
- fewer Th
- thymic involution
- more autoimmune diseases
What is the Rate of Living Theory?
greater basal O2 metabolism = shorter lifespan
– supported by caloric restriction studies
What is the Failure of Neurogenesis theory?
based on finding that neurogenesis required throughout life in some parts of brain
- hippocampus
- olfactory bulb
- crucial for synaptic plasticity (learning, memory)
What theory of aging has the best evidence?
free radical theory
What are the Damage theories?
1) free radical
2) failure of endogenous repair
3) failure of neurogenesis
4) environmental exposures
5) rate of living
6) wear and tear
What is the failure of endogenous repair mechanisms theory?
environmental exposures neutralized by neurotrophins, DNA repair, etc.
- neurotrophins turned off during CNS development
- turned on after trauma/toxicity
What is the free radical theory?
slow persistent accumulating DNA/protein/lipid damage
– mitochondrial death switch
What is nuclear compaction?
process that occurs in apoptosis
- chromatin condensation
- DNA cleavage
- formation of apoptotic bodies
Why is apoptosis better?
plasma membrane stays intact
– minimal inflammatory response
What substances induce necrosis?
trauma, toxins, hypoxia
Ca overload, oxidative stress
– cellular swelling causes rupture of all membranes
What causes secondary brain damage?
microglia scavenging remainders of cell death
– apoptosis and necrosis
What defends against ROS?
enzymes
– SOD, GSH peroxidase, catalase
antioxidants
– GSH, polyphenols, Vit. E + C
Why are neurons especially vulnerable to ROS?
1) high demand
- - many cells, long axons
2) little capacity to make/store energy
3) metabolic demands increase with age
SOD:
O2. (superoxide) – H2O2
Fe catalyzes:
H2O2 – OH. (hydroxyl radical)
the fenton reaction
GSH Peroxidase catalyzes:
H2O2 – H2O
Catalase catalyzes:
H2O2 – H2O + O2
What disease has an SOD mutation?
ALS
O2. + NO. (from Arg) –
ONOO- (peroxynitrite)
