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Disease, Diagnostics and Therapeutics > Frailty > Flashcards

Frailty Flashcards

1
Q

what is the tertiary protein structure

A

three-dimensional folding pattern of a protein due to side chain interactions

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2
Q

How does the endocrine system contribute to sarcopenia

A
  • Increased IR
  • Decreased GH
  • Reduced oestrogen and testosterone
  • Vitamin D deficiency- increases osteoporosis
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3
Q

What is the quaternary protein structure

A

protein consisting of more than one amino acid chain

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4
Q

Give 2 characteristics of type 2b fast glycolytic twitch muscle fibres

A

Highest myosin ATPase activity
Lowest capacity for ATP production (via oxidative phosphorylation)
No intracellular myoglobin
Very high force production

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5
Q

What replaces muscle mass in older people

A

increased fat mass

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6
Q

Give 2 characteristics of type 2a fast oxidative twitch muscle fibres

A

Higher myosin ATPase activity than type 1 fibres
High capacity for ATP production (via oxidative phosphorylation)
High levels of intracellular myoglobin
Medium-high force production

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7
Q

What is the role of the Ubiquitinating enzymes

A

(UBEs) catalyse protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action.

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8
Q

What is the effect of myostatin

A

prevents muscle growth via atrogene transcription

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9
Q

Define inflammaging

A

chronic progressive increase in the proinflammatory status because of ageing.

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10
Q

What are the names of the two steps in the UPP

A

Conjugation and degradation

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11
Q

Aged 75+, what does % of mass does lean muscle contribute to

A

25%

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12
Q

When mTOR from the PI3K/AKT pathway activates mTORC2 rictor, what happens

A

activates Akt, which indirectly activate mTORC1 raptor

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13
Q

What is the primary protein structure

A

sequence of a chain of amino acids

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14
Q

How is the resting membrane potential of synapses affected by age

A

Decreased

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15
Q

Define sarcopenia

A

loss of muscle mass, strength and quality

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16
Q

What does mTOR2 rictor activate

A

Akt

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17
Q

How is the resting membrane potential of nerve cells affected by age

A

It isn’t

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18
Q

Describe the hallmark of ageing: Stem Cell Exhaustion

A
  • Haematopoiesis declines
  • reduced production of adaptive immune cells- immunosenescence
  • Older stem cells undergo fewer divisions than newer cells
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19
Q

How many lysine residues does ubiquitin have

A

7

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20
Q

Describe the hallmark of ageing: epigenetic alteration

A

histone modifications & DNA methylation

Changed gene expression.

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21
Q

Describe the hallmark of ageing: loss of proteostasis

A

-Chronic expression of mis or unfolded proteins

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22
Q

what does Akt inhibit

A

inhibits FOXO - transcription factor
- genes involved in autopahgy and protein degredation

inactives Bad
- bad is part of a complex with a protein which inhibits apoptosis, by inhibiting Bad, it allows the protein to be active

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23
Q

What is mTOR

A

It is a mammalian target of rapamycin- an immunosuppressant.
It is a key regulator of normal cellular processes involved with cell growth, proliferation, motility, and apoptosis.

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24
Q

What happens to ubiquitylated proteins

A

bind to the proteasome which removes the ubiquitin tag (deubiquitylation),
unfolds the proteins,
transports it into its proteolytic chamber
and chops it into small peptide fragments

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25
Q

Define immunosenescence

A

the gradual deterioration/dysregulation of the immune system caused by natural age advancement

26
Q

What are the three characteristics of an action potential

A

discreet, all-or-nothing, or unidirectional

27
Q

Local folding of the polypeptide chain into helices or sheets is what

A

Secondary protein structure

28
Q

Which fibre type specifically shows the greatest reduction in older people

A

type 11b glycolytic fibres

29
Q

How can Akt indirectly activate mTORc1

A

phosphorylating and inactivating Rheb-GAP. Inactivated Rheb-GAP prevents activity of GTPase. So, by inactivating Rheb, it activates mTORC1.

30
Q

Explains the steps of the IGF/Akt pathway

A

Growth factor binds to tyrosin kinase molecule
receptor dimersiation and conformational change
transautophossphorylation
sticky patches attracts SH2 of PI3K
phosphorylates PIP2 to PIP3
PIP3 recruits protiens with particular binding sites - PH
PIP3 recruits PDK1
phosphorylates Akt
Akt binds to PIP3
Akt further phosphorylates mTOR
Akt now super active, phosphorylates others
kinase cascade

31
Q

What happens at +30mV in an action potential

A

VG NA close, VG K open and K repolarises the cell

32
Q

Give 2 characteristics of type 1 slow twitch muscle fibres

A

Low myosin ATPase activity
High capacity for ATP production (via oxidative phosphorylation)
High levels of intracellular myoglobin
Low force production

33
Q

Define cellular senescence

A

stable arrest of cell cycle

34
Q

What are the 5 states of inflammaging

A
  1. Low grade
  2. Controlled
  3. Asymptomatic
  4. Chronic
  5. Systemic
35
Q

Describe the hallmark of ageing: Telomere attrition

A
  • DNA ends can’t be replicated

- Telomere shortening

36
Q

What are the three classes of enzymes used in the UPP

A
  1. A “ubiquitin activating enzyme” (E1)
  2. A “ubiquitin conjugating enzyme” (E2)
  3. A “ubiquitin ligase” (E3)
37
Q

What is the Ubiquitin Proteasome Pathway

A

the principal mechanism for protein catabolism in the mammalian cytosol and nucleus.

38
Q

How does smooth muscle change with age

A

the blood vessel wall broadens and develops a thickened intima.
Stiffens due to collagen

39
Q

What comprises protein structure

A

The number, sequence, and 3D structure of amino acids

40
Q

Define programmed longevity

A

sequential switching on and off of switches over time causes deterioration

41
Q

Define autophagy

A

‘self-eating’ using lysosomes to cause cell death.

Its nonapoptotic programmed cell death with different pathways and mediators from apoptosis.

42
Q

Describe the hallmark of ageing: Genomic instability

A

-Accumulate genetic damage throughout life

43
Q

What is a cDNA library

A

the complementary DNA which is reverse transcribed from the expressed mRNA.

44
Q

what is IGF

A

a signalling molecule that binds to tyrosine kinase molecule

45
Q

What repolarises the cell after hyperpolarisation

A

The Na/K pump

46
Q

What causes the long APs in cardiac myocytes?

A

Ca2+ entry through VG-channels, both from the SR and extracellularly. This provides a longer contraction.

47
Q

Describe the hallmark of ageing: Cellular Senescence

A
  • Caused by telomere shortening and DNA damage
  • leads to stem cell exhaustion
  • inflammaging
48
Q

What are the effects of mTOR raptor activation

A

increase in cell growth, ribosome production, protein synthesis, nutrient uptake, and the inhibition on proteolysis.

49
Q

What is the approximate resting membrane potential of a neuron

A

-70mV

50
Q

What are the ubiquitin lysine residues for

A

involved in linking multiple Ub polypeptides together to form a polyubiquitin chain.

51
Q

What is ubiquitylation

A

Proteins that must be degraded are tagged with a small protein called ubiquitin

52
Q

Describe the hallmark of ageing: Mitochondrial dysfunction

A
  • increasing electron leakage and reducing ATP generation

- ROS production causes ageing

53
Q

Describe the hallmark of ageing: Altered intercellular communication

A
  • Neurohormonal signalling deregulated in ageing
  • Age-related changes in one tissue can lead to ageing specific deterioration in other tissues (via gap junctions and ROS processes)
54
Q

Explain the steps in IRS-1 binding

A

IRS-1 is recruited by its PH/PTB domains and phosphorylated in tyrosine residues, by upstream tyrosine kinase receptors.

Tyrosine phosphorylated IRS1 binds to signalling effectors and activates signalling cascades, which regulate proliferation and survival of cells.

55
Q

True or false: Ageing causes decreased synaptic excitation but increased synaptic inhibition

A

True

56
Q

What does % of mass does lean muscle contribute to in young adults

A

50%

57
Q

what is ubiquitin

A

a polypeptide which acts as a molecular label within the UPS

58
Q

What does age-related axonal sprouting cause (APs)

A

tendency to increase AP amplitude in slow twitch muscle

59
Q

Give 3 processes the UPP is central for

A
  • Apoptosis
  • Biogenesis of organelles
  • Cell cycle and division
  • DNA transcription and repair
  • Immune response and inflammation
  • Neural and muscular degeneration
60
Q

What happens at -55mV in an action potential

A

voltage gated Na channels open and flood into the cell. Depolarisation

61
Q

Describe the hallmark of ageing: Deregulated nutrient sensing

A

Reduced IGF-1, so less protein synthesis

62
Q

What is the function of a chaperonin

A

binds to new chain (from ribosome) to help with protein folding

Disease, Diagnostics and Therapeutics (14 decks)

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