Free Radical Theory of Ageing

Question 1

Define the free radical theory of ageing.

Answer 1

Ageing results from deleterious effects of free radicals produced in the course of cellular metabolism.

Question 2

What conditions must be met for the free radical theory of ageing to hold?

Answer 2

Increased ROS generation with age.
Levels of oxidised biomolecules should increase with age.
Manipulations increasing lifespan should diminish oxidative injury.
Decreasing OS levels should retard ageing and increase lifespan.

Question 3

What is the maillard reaction?

Answer 3

Carbonyl group of sugar + amino group of an AA –> N substituted glycosylamine.
Can then from a ketosamine which can further react to become carcinogenic.
As we age glucose undergoes addition to form products promoted covalent linkage with other glaciated proteins.

Question 4

What are the effects of AGE’s?

Answer 4

Random protein aggregation 
Proteins can't be degraded. 
Yellows nails and teeth 
Ageing of skin (binds collagen) 
Rigidity of RBCs / arterial stiffness
More rigid blood vessels.

Question 5

What is the mitochondrial theory of ageing?

Answer 5

High []s mtDNA oxidation –> shorter lives.
TBARS - as increase mt enzyme function decreases. and loss of enzyme function associated with decreases in memory, muscle strength and lifespan.

Question 6

What evidence suggests that the maillard reaction may affect functional decline in ageing?

Answer 6

Isolate B cells from pancreas and treat either with BSA or BSA-AGE –> BSA-AGE treated cells have increased mt superoxide production,, reduced plc stimulated insulin secretion and decreased ATP.
Addition of ALT (cleaves AGE from BSA) –> restoration of function.

Question 7

What is the phenotype of age-1 mutants of C. Elegans?

Answer 7

Enhanced CuZnSOD and catalase.
More resistant to H2O2, paraquat.
Slower age-related protein carbonyl accumulation.