Biology of Ageing 1

Question 1

specific types of intracellular degradation

Answer 1

aggrephagy
lysophagy
ribophagy
mitophagy
ferritinophagy
reticulophagy, nucleophagy
xenophagy
proteophagy
lipophagy
pexophagy

Question 2

types of DNA repair that occurs in response to:
- base mismatch
- ss break/damage
- bulky lesion/crosslinks
- ds breaks

Answer 2

• base mismatch - mismatch repair
• ss break/damage - base excision repair
• bulky lesion/crosslinks - nucleotide excision repair
• ds breaks - homologous recombination/non-homologous end joining

Question 3

what are the two main theories of ageing and what they mean
examples of each

Answer 3

program theories of ageing: fundamental limitation (telomere attrition, stem cell exhaustion)

damage theories of ageing: deterioration accumulation (mitochondrial dysfunction, chronic inflammation)

Question 4

program theories of ageing

Answer 4

irreversible process controlled by internal factors that we can only slow down

Question 5

damage theories of ageing

Answer 5

reversible process affected by external factors that can be rejuvenated when we remove the risk factors

Question 6

how does deterioration accumulation lead to fundamental limitation

Answer 6

mitochondrial dysfunction leads to chronic inflammation
increased immune cell activation leads to proliferation and differentiation
leads to telomere attrition with every division
leads to stem cell exhaustion

Question 7

primary hallmarks of ageing

Answer 7

genomic instability
telomere attrition
epigenetic alterations
loss of proteostasis
disabled macroautophagy

Question 8

antagonistic hallmarks of ageing

Answer 8

cellular senescence
mitochondrial dysfunction
dysregulated nutrient sensing

Question 9

integrative hallmarks of ageing

Answer 9

stem cell exhaustion
altered intracellular communication
chronic inflammation
dysbiosis

Question 10

why do humans have longer spans than mice despite having shorter telomeres

Answer 10

shortening rate predicts species life span not starting length

Question 11

methods of telomere length measurement

Answer 11

southern blotting gel
Q-PCR (due to repetitive DNA seq)
genome wide sequence
fluorescence in situ hybridisation

Question 12

what happens when p53 is stabilised by mutation
what statement does this prove

Answer 12

remain cancer free for longer but die sooner due to senescence

tumour suppressors drive cellular senescence

Question 13

early ageing-related phenotype mouse

Answer 13

reduced body size and kyphosis present (excessive rounding of upper back)
reduction in cortical bone thickness and absence of trabecular bone
osteoporosis and muscle atrophy so shape cannot be held well

Question 14

beneficial consequences of cell senescence

Answer 14

embryonic development
wound healing and regeneration
tumour suppression

Question 15

ambiguous consequences of cell senescence

Answer 15

reprogramming

Question 16

deleterious consequences of cell senescence

Answer 16

tumour development
stem cell exhaustion