L17: nutrition and the ageing heart Flashcards
What does a cardiomyocyte exist of ?
cardiomyocyte exists of myofibrils, mito’s and sarcoplasmic reticulum
Descending order in size, structural layers of the heart?
Myocardium = layer heart wall
Cardiomyocyte = ‘bands existing of..
..Myofibril’
Sarcomeres
Filaments
What is the basic contractile unit of the myocardium?
Sarcomere
Filaments of the sarcomere: which types are there and what do they exist of?
- Thick filament = mainly myosin
- Thin filament = mainly composed of actin
When contracting, there is a change in length of filaments
true/false
false
Which filament protein is responsible for force generation?” Why?
“Myosin” Thick filament
Only myosin has ATPase. Not actin.
ATP is needed for sarcomere
shortening
Without calcium, no contraction. Why?
Binding of calcium to tropomyosin is needed for conformational change and contraction. No calcium = no contraction. (Calcium binds to actin sites that myosin needs to bind to, I think).
So, what are the key playersn up until now?
ATP + calcium
Excitation-contraction (EC) coupling
= ?
Mechanism by which plasma membrane depolarization initiates contraction. Dependent on calcium .
1. Action potential
2. Calcium peak
3. Contraction
What is the ageing effect on cardiac calcium?
Ageing is associated with deterioration of calcium homeostasis: reduced Calcium amplitude (peak).
Also associated with a delayed calcium decay or prolonged peak duration
Cardiac energy metabolism: 3 paths
- Substrate utilization (beta-ox, TCA cycle)
- Oxidative phosphorylation
- Energy transfer and utilization (Phosphocreatine)
How does ageing affect the level of energy?
Cardiac energy reserve declines with normal ageing (less pCr)
Ageing is associated with mitochondrial dysfunction and impaired ATP production. Volume of mito’s also decreases.
Heart hallmarks of ageing on four levels:
1. Functional
2. Structural
3. Cellular
4. Molecular
Give examples
- Heart is not able to relax as much (diastolic dysfunction)
- Hypertrophy (thicker wall), fibrosis
3 & 4. Mito dysfunctioning, ox stress, inflammation, apoptosis, lipofuscin accumulation
What are the most common age-related heart diseases in humans?
Arrythmia (atrial fibrillation) and heart failure (HFpEF)
Age = dominant risk factor for development of CVD
What is the ejection fraction?
Ratio of pumped blood to total volume in ventricle = ejection fraction.
What is a normal ejection fraction?
> 50%
What is - Heart failure reduced ejection fraction (HFrEF)?
ejection fraction <40%, meaning there is not enough blood that is pumped out by the heart.
What is - Heart failure preserved ejection fraction (HFpEF)?
(HFpEF), also referred to as diastolic heart failure, is
characterized by signs and symptoms of heart failure and a left ventricular ejection fraction (LVEF)
greater than 50%.
HFpEF = leading cause of hospitalization in elderly
true/false
true
Compared with HFrEF, there are evidence-based therapies for HFpEF
true/false
false: there are no evidence-based therapies
HFrEF medications failed to improve mortality in patients with HFpEF
true/false
true
Diastolic dysfunction is not the same as diastolic HF (HFpEF). However they both have problems with relaxation of the heart. Degree is different.
Explain
Diastolic dysfunction is something you have with ageing, but not all ageing people have diastolic HF (= HFpEF), this is more severe.
Why is autophagy important for post-mitotic cells such as cardiomyocytes?
Bc they cannot devide, usually you have new cells that will be healthy and the old cells will go to apoptosis. But now they don’t devide, cells have a lot of toxic protiens, organ will die
Steps of autophagy?
Autophagy: ->
Atg5 protein = needed
to initiate autophagy
(phagophore)
Then, autophagosome
needs to mature
Then, autolysosome is formed
Autophagy is regulated by molecular pathways of longevity, learned from calorie restriction studies
ok
Longevity pathways: which are inhibiting and which are inducing?
1 MAmmalian target of rapamycin (mTOR) patway
2 Growth hormone/IGF-1 pathway/AKT pathway
3 Sirtuins
4 AMP-activated protein kinase (AMPK)
1,2: inhibiting
3,4: inducing
What lifestyle modifications increase autophagy?
Caloric restriction, intermittent fasting, exercise
Two most important (or discussed) nutrients that increase autophagy and mimic caloric restriction?
Spermidine & NAD+ precursors
Spermidine: what does it do?
- improves cardiac diastolic function in aged mice through induction of autophagy
- inversely correlates with human cardioascular disease and death.
