Frailty Flashcards
what is the tertiary protein structure
three-dimensional folding pattern of a protein due to side chain interactions
How does the endocrine system contribute to sarcopenia
- Increased IR
- Decreased GH
- Reduced oestrogen and testosterone
- Vitamin D deficiency- increases osteoporosis
What is the quaternary protein structure
protein consisting of more than one amino acid chain
Give 2 characteristics of type 2b fast glycolytic twitch muscle fibres
Highest myosin ATPase activity
Lowest capacity for ATP production (via oxidative phosphorylation)
No intracellular myoglobin
Very high force production
What replaces muscle mass in older people
increased fat mass
Give 2 characteristics of type 2a fast oxidative twitch muscle fibres
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
What is the role of the Ubiquitinating enzymes
(UBEs) catalyse protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action.
What is the effect of myostatin
prevents muscle growth via atrogene transcription
Define inflammaging
chronic progressive increase in the proinflammatory status because of ageing.
What are the names of the two steps in the UPP
Conjugation and degradation
Aged 75+, what does % of mass does lean muscle contribute to
25%
When mTOR from the PI3K/AKT pathway activates mTORC2 rictor, what happens
activates Akt, which indirectly activate mTORC1 raptor
What is the primary protein structure
sequence of a chain of amino acids
How is the resting membrane potential of synapses affected by age
Decreased
Define sarcopenia
loss of muscle mass, strength and quality
What does mTOR2 rictor activate
Akt
How is the resting membrane potential of nerve cells affected by age
It isn’t
Describe the hallmark of ageing: Stem Cell Exhaustion
- Haematopoiesis declines
- reduced production of adaptive immune cells- immunosenescence
- Older stem cells undergo fewer divisions than newer cells
How many lysine residues does ubiquitin have
7
Describe the hallmark of ageing: epigenetic alteration
histone modifications & DNA methylation
Changed gene expression.
Describe the hallmark of ageing: loss of proteostasis
-Chronic expression of mis or unfolded proteins
what does Akt inhibit
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
What is mTOR
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.
What happens to ubiquitylated proteins
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
Define immunosenescence
the gradual deterioration/dysregulation of the immune system caused by natural age advancement
What are the three characteristics of an action potential
discreet, all-or-nothing, or unidirectional
Local folding of the polypeptide chain into helices or sheets is what
Secondary protein structure
Which fibre type specifically shows the greatest reduction in older people
type 11b glycolytic fibres
How can Akt indirectly activate mTORc1
phosphorylating and inactivating Rheb-GAP. Inactivated Rheb-GAP prevents activity of GTPase. So, by inactivating Rheb, it activates mTORC1.
Explains the steps of the IGF/Akt pathway
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
What happens at +30mV in an action potential
VG NA close, VG K open and K repolarises the cell
Give 2 characteristics of type 1 slow twitch muscle fibres
Low myosin ATPase activity
High capacity for ATP production (via oxidative phosphorylation)
High levels of intracellular myoglobin
Low force production
Define cellular senescence
stable arrest of cell cycle
What are the 5 states of inflammaging
- Low grade
- Controlled
- Asymptomatic
- Chronic
- Systemic
Describe the hallmark of ageing: Telomere attrition
- DNA ends can’t be replicated
- Telomere shortening
What are the three classes of enzymes used in the UPP
- A “ubiquitin activating enzyme” (E1)
- A “ubiquitin conjugating enzyme” (E2)
- A “ubiquitin ligase” (E3)
What is the Ubiquitin Proteasome Pathway
the principal mechanism for protein catabolism in the mammalian cytosol and nucleus.
How does smooth muscle change with age
the blood vessel wall broadens and develops a thickened intima.
Stiffens due to collagen
What comprises protein structure
The number, sequence, and 3D structure of amino acids
Define programmed longevity
sequential switching on and off of switches over time causes deterioration
Define autophagy
‘self-eating’ using lysosomes to cause cell death.
Its nonapoptotic programmed cell death with different pathways and mediators from apoptosis.
Describe the hallmark of ageing: Genomic instability
-Accumulate genetic damage throughout life
What is a cDNA library
the complementary DNA which is reverse transcribed from the expressed mRNA.
what is IGF
a signalling molecule that binds to tyrosine kinase molecule
What repolarises the cell after hyperpolarisation
The Na/K pump
What causes the long APs in cardiac myocytes?
Ca2+ entry through VG-channels, both from the SR and extracellularly. This provides a longer contraction.
Describe the hallmark of ageing: Cellular Senescence
- Caused by telomere shortening and DNA damage
- leads to stem cell exhaustion
- inflammaging
What are the effects of mTOR raptor activation
increase in cell growth, ribosome production, protein synthesis, nutrient uptake, and the inhibition on proteolysis.
What is the approximate resting membrane potential of a neuron
-70mV
What are the ubiquitin lysine residues for
involved in linking multiple Ub polypeptides together to form a polyubiquitin chain.
What is ubiquitylation
Proteins that must be degraded are tagged with a small protein called ubiquitin
Describe the hallmark of ageing: Mitochondrial dysfunction
- increasing electron leakage and reducing ATP generation
- ROS production causes ageing
Describe the hallmark of ageing: Altered intercellular communication
- 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)
Explain the steps in IRS-1 binding
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.
True or false: Ageing causes decreased synaptic excitation but increased synaptic inhibition
True
What does % of mass does lean muscle contribute to in young adults
50%
what is ubiquitin
a polypeptide which acts as a molecular label within the UPS
What does age-related axonal sprouting cause (APs)
tendency to increase AP amplitude in slow twitch muscle
Give 3 processes the UPP is central for
- Apoptosis
- Biogenesis of organelles
- Cell cycle and division
- DNA transcription and repair
- Immune response and inflammation
- Neural and muscular degeneration
What happens at -55mV in an action potential
voltage gated Na channels open and flood into the cell. Depolarisation
Describe the hallmark of ageing: Deregulated nutrient sensing
Reduced IGF-1, so less protein synthesis
What is the function of a chaperonin
binds to new chain (from ribosome) to help with protein folding
