19. ageing biology 5 Flashcards

1
Q

why are studies on people that live for a very long time hard? (3)

A

they are hard to organise, expensive and run over many years

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2
Q

how many people live over 100?

A

1 in 5000

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3
Q

how many people live over 110?

A

1 in 5 million

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4
Q

what is presumed about people that live over 110?

A

there is something special about their genome and cellular biology, as it is unlikely that they have been protected from environmental stresses during this time

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5
Q

what percentage of how long we live is down to genetics, and what does this increase to after the age of 85?

A

20-30%

40%

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6
Q

GWAS of people that are very old are difficult due to what factor?

A

lack of control groups

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7
Q

what can be done to overcome this GWAS difficulty? (even if it is not ideal)

A

looking at the offspring of those that live long and those that don’t and comparing their genomes to look for genetic components involved

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8
Q

which gender live longer and why is this becoming less apart?

A

women on average live longer, but now we are post-industrial and men have less risky jobs

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9
Q

what was seen in the serum of offspring of centenarians? and what polymorphism was observed?

A

35% higher serum IGF1

a slight loss of function of IGFR1 which results in reduced phosphorylation of Akt and dampening of metabolism

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10
Q

what was seen in some Japanese semisupercentenarians? and what did this suggest?

A

one form of INSR (insulin receptor)
this suggests that there is something about insulin signalling and nutrient sensing that is crucial for lifespan regulation

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11
Q

what genes that are related to insulin signalling have intronic SNPs been identified in that are associated with long life?

A

AKT1 and FOXO3A

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12
Q

what are the limitations of lots of these studies?

A

they identify genes associated with people that live longer than others but don’t necessarily determine how this affects molecular biology of their cells

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13
Q

long lived males in Hawaii had SNP associated with what gene?

A

FOXO3

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14
Q

what was also interesting about these long lived Hawaiian men? and what did this suggest?

A
  • they had less cancer and cardiovascular disease, they felt healthier and had good physical and cognitive function
  • this suggests that they have more robust stress responses
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15
Q

particular alleles of what genes have been linked with long life? (5) and what does this suggest?

A

ApoA, LMNA, WNR, SOD1 and SOD2

this suggests that ageing is not down to one gene, it is down to a combination of genes

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16
Q

what three things seems to play an important role in the ageing process?

A
  1. genomic stability
  2. insulin signalling
  3. proteostasis
17
Q

what happens to telomeres as we age?

A

they get shorter, this is especially bad when it occurs in stem cells

18
Q

what happens to proteostasis as we age?

A

it become less efficient, you stop being able to regulate proteins folding regulation and degradation

19
Q

what does the ageing process involve at the cellular level? (9)

A
  1. genetic instability
  2. telomere attrition
  3. epigenetic alterations
  4. loss of proteostasis
  5. deregulated nutrient sensing
  6. deregulated nutrient sensing
  7. cellular sensence
  8. stem cell exhaustion
  9. altered intercellular communication
20
Q

describe some potential therapeutic targets for symptoms of ageing that makes ageing a potentially ‘curable disease’ (7)

A
  • clearance of senescent cells
  • stem cell based therapies
  • anti-inflammatories
  • telomerase reactivation
  • activation of protein chaperones
  • dietary restriction
  • mitophagy