Free Radical Theory of Ageing Flashcards
Define the free radical theory of ageing.
Ageing results from deleterious effects of free radicals produced in the course of cellular metabolism.
What conditions must be met for the free radical theory of ageing to hold?
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.
What is the maillard reaction?
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.
What are the effects of AGE’s?
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.
What is the mitochondrial theory of ageing?
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.
What evidence suggests that the maillard reaction may affect functional decline in ageing?
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.
What is the phenotype of age-1 mutants of C. Elegans?
Enhanced CuZnSOD and catalase.
More resistant to H2O2, paraquat.
Slower age-related protein carbonyl accumulation.