Ageing Flashcards
Define ageing
Intrinsic deterioration processleading to impairment of function, increasing vulnerability to environmental challenge, increased likelihood of death and a decline in fertility.
Is ageing genetic?
Positive correlation between longevity of parents and offspring, suggesting a genetic component
What did Haldane conclude re ageing?
Natural selection cannot easily remove late-acting deleterious mutations from a population.
Ageing is the inevitable result of the declining force of natural selection with age
What theories exist to explain ageing?
Antagonistic Pleiotrophy
Disposable Soma Theory
What is the theory of antagonistic Pleiotrophy and the evidence supporting it?
Predicts that organisms that have high fecundity when young will have shortened lifespan and vice versa
Support: D melanogaster flies selected for longer life span experienced a reduction in early fecundity. Mortality rate increased more slowly with age compared to control flies
What is the Disposable Soma theory and the evidence that supports it?
Predicts that the proportion of effort devoted to cellular maintenance and repair will vary with longevity
What are the hallmarks of ageing?
Genomic instability Telomere attrition Epigenetic alteration Loss of proteostasis Deregulated nutrient sensing Mitochondrial dysfunction cellular senescence stem cell exhaustion altered intercellular communication
What factors lead to cellular ageing?
Cells accumulate damage as the organism ages
Capacity to replace damaged cells declines
How are cells damaged?
Intrinsic factors; ROS, telomere erosion, replication fork stalling, etc
Extrinsic factors; radiation, chemical mutagens, etc
What is the fate of damaged cells?
Repair
Senescence
Death (apoptosis/necrosis)
How can ROS lead to DNA damage?
8-oxoguanine can be incorporated into DNA without blocking DNA synthesis, but can pair with either C or A, so can be mis-incorporated opposite C or A.
DNA mismatch repair could repair correctly orincorrectly, leading to DNA mutation.
What is the relationship between metabolic rate, ROS production and lifespan?
Some evidence supporting theory that lower metabolic rate = reduced ROS production = increased lifespan
What is the relationship between mitochondrial function and ageing?
Evidence that mitochondrial mutations = increased ROS production BUT =/= ageing
From altering proof-reading ability of DNA polymerase.
Therefore mitochondrial dyspfunction contributes to ageing via other pathways more than via ROS.