L17: nutrition and the ageing heart

Question 1

What does a cardiomyocyte exist of ?

Answer 1

cardiomyocyte exists of myofibrils, mito’s and sarcoplasmic reticulum

Question 2

Descending order in size, structural layers of the heart?

Answer 2

Myocardium = layer heart wall
Cardiomyocyte = ‘bands existing of..
..Myofibril’
Sarcomeres
Filaments

Question 3

What is the basic contractile unit of the myocardium?

Answer 3

Sarcomere

Question 4

Filaments of the sarcomere: which types are there and what do they exist of?

Answer 4

• Thick filament = mainly myosin
• Thin filament = mainly composed of actin

Question 5

When contracting, there is a change in length of filaments
true/false

Answer 5

false

Question 6

Which filament protein is responsible for force generation?” Why?

Answer 6

“Myosin” Thick filament
 Only myosin has ATPase. Not actin.
 ATP is needed for sarcomere
shortening

Question 7

Without calcium, no contraction. Why?

Answer 7

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).

Question 8

So, what are the key playersn up until now?

Answer 8

ATP + calcium

Question 9

Excitation-contraction (EC) coupling
= ?

Answer 9

Mechanism by which plasma membrane depolarization initiates contraction. Dependent on calcium .
1. Action potential
2. Calcium peak
3. Contraction

Question 10

What is the ageing effect on cardiac calcium?

Answer 10

 Ageing is associated with deterioration of calcium homeostasis: reduced Calcium amplitude (peak).
 Also associated with a delayed calcium decay or prolonged peak duration

Question 11

Cardiac energy metabolism: 3 paths

Answer 11

1. Substrate utilization (beta-ox, TCA cycle)
2. Oxidative phosphorylation
3. Energy transfer and utilization (Phosphocreatine)

Question 12

How does ageing affect the level of energy?

Answer 12

 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.

Question 13

Heart hallmarks of ageing on four levels:
1. Functional
2. Structural
3. Cellular
4. Molecular

Give examples

Answer 13

1. Heart is not able to relax as much (diastolic dysfunction)
2. Hypertrophy (thicker wall), fibrosis
   3 & 4. Mito dysfunctioning, ox stress, inflammation, apoptosis, lipofuscin accumulation

Question 14

What are the most common age-related heart diseases in humans?

Answer 14

 Arrythmia (atrial fibrillation) and heart failure (HFpEF)
 Age = dominant risk factor for development of CVD

Question 15

What is the ejection fraction?

Answer 15

Ratio of pumped blood to total volume in ventricle = ejection fraction.

Question 16

What is a normal ejection fraction?

Answer 16

> 50%

Question 17

What is - Heart failure reduced ejection fraction (HFrEF)?

Answer 17

ejection fraction <40%, meaning there is not enough blood that is pumped out by the heart.

Question 18

What is - Heart failure preserved ejection fraction (HFpEF)?

Answer 18

(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%.

Question 19

HFpEF = leading cause of hospitalization in elderly
true/false

Answer 19

true

Question 20

Compared with HFrEF, there are evidence-based therapies for HFpEF
true/false

Answer 20

false: there are no evidence-based therapies

Question 21

HFrEF medications failed to improve mortality in patients with HFpEF
true/false

Answer 21

true

Question 22

 Diastolic dysfunction is not the same as diastolic HF (HFpEF). However they both have problems with relaxation of the heart. Degree is different.

Explain

Answer 22

 Diastolic dysfunction is something you have with ageing, but not all ageing people have diastolic HF (= HFpEF), this is more severe.

Question 23

Why is autophagy important for post-mitotic cells such as cardiomyocytes?

Answer 23

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

Question 24

Steps of autophagy?

Answer 24

Autophagy: ->
Atg5 protein = needed
to initiate autophagy
(phagophore)

Then, autophagosome
needs to mature

Then, autolysosome is formed

Question 25

Autophagy is regulated by molecular pathways of longevity, learned from calorie restriction studies

Answer 25

ok

Question 26

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)

Answer 26

1,2: inhibiting
3,4: inducing

Question 27

What lifestyle modifications increase autophagy?

Answer 27

Caloric restriction, intermittent fasting, exercise

Question 28

Two most important (or discussed) nutrients that increase autophagy and mimic caloric restriction?

Answer 28

Spermidine & NAD+ precursors

Question 29

Spermidine: what does it do?

Answer 29

• improves cardiac diastolic function in aged mice through induction of autophagy
• inversely correlates with human cardioascular disease and death.