Ageing Flashcards

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1
Q

Define ageing

A

Intrinsic deterioration processleading to impairment of function, increasing vulnerability to environmental challenge, increased likelihood of death and a decline in fertility.

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2
Q

Is ageing genetic?

A

Positive correlation between longevity of parents and offspring, suggesting a genetic component

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3
Q

What did Haldane conclude re ageing?

A

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

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4
Q

What theories exist to explain ageing?

A

Antagonistic Pleiotrophy

Disposable Soma Theory

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5
Q

What is the theory of antagonistic Pleiotrophy and the evidence supporting it?

A

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

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6
Q

What is the Disposable Soma theory and the evidence that supports it?

A

Predicts that the proportion of effort devoted to cellular maintenance and repair will vary with longevity

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7
Q

What are the hallmarks of ageing?

A
Genomic instability
Telomere attrition
Epigenetic alteration
Loss of proteostasis
Deregulated nutrient sensing
Mitochondrial dysfunction
cellular senescence
stem cell exhaustion
altered intercellular communication
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8
Q

What factors lead to cellular ageing?

A

Cells accumulate damage as the organism ages

Capacity to replace damaged cells declines

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9
Q

How are cells damaged?

A

Intrinsic factors; ROS, telomere erosion, replication fork stalling, etc
Extrinsic factors; radiation, chemical mutagens, etc

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10
Q

What is the fate of damaged cells?

A

Repair
Senescence
Death (apoptosis/necrosis)

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11
Q

How can ROS lead to DNA damage?

A

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.

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12
Q

What is the relationship between metabolic rate, ROS production and lifespan?

A

Some evidence supporting theory that lower metabolic rate = reduced ROS production = increased lifespan

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13
Q

What is the relationship between mitochondrial function and ageing?

A

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.

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