Cardiovascular ageing: mechanisms
14 important questions on Cardiovascular ageing: mechanisms
What is the strucute of the whole heart?
- Aorta
- pulmonary artery
- auricle of left atrium
- coronary artery and vein
- left ventricle
- right ventricle
- right atrium
- superior vena cava
This is how the whole heart looks like, mainly consist of 4 parts: LV,LA, RV and RA. We often think the heart as “muscular pump” which pumps blood to your body
What is the structure of the cardiac muscle (myocardium)
- Myocytes
- Intercalated disks
Here on the left is a cross-sectional picture of the heart. The myocardium or the cardiac muscle wall of the heart is the one that generate force. Let’s zoom in the myocardium and then you can see they are mainly made of cardiac muscle cells, in short cardiomyocytes, which are connected with each other via the intercalated disks.
What is the ultrastructure of the cardiomyocyte?
- Myofibrils
- mitochondria
- sarcoplasmic reticulum
M: mitochondria
SR: sarcoplasmic reticulum
The myofibrils are contractile proteins including thick and thin filaments which make up almost half of the cell volume. Most of the remaining cell volume is occupied by mitochondria, which generate the large amount of high-energy phosphate required for contraction. SR store a lot of calcium, which is important for initiate the contraction.
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What is the effect of ageing on cardiac calcium?
- reduced CaT amplitude
- delayed CaT decay or prolonged CaT duration
Calcium is measured in isolated human right atrial myocytes. These observation showed a three-fold reduction of the calcium transient amplitude and slowing of its decay in patients older than 75 years, which may favor a progressive decline in atrial contractile function with age.
How can ATP and pCr be measured in in vivo
PCr and ATP can be measured in vivo by the 31P magnetic resonance spectroscopy. Here is an example of the the spectrum of a normal person. You see higher peak of PCr than the ATP.
What declines with normal ageing?
With ageing, you see a decline of PCr. Here on the left you see sample cardiac phosphorus spectra from a young subject (with PCr/ ATP =1.95) and an older subject (with PCr/ATP = 1.55). A difference in PCr concentration is seen. 2,3-DPG, 2,3-diphosphoglycerate; ppm, parts/million; PDE, phosphodiesters. cardiac energetics represented by the ratio of phosphocreatine to ATP (PCr/ATP ratio
Where is the Drosophila model used for
Using the drosophila model, serval redearchers such as ocorr et al found that old flies are associated with increased heart failure rate induced by stress and also increased arrhythmicity.
What are the two most common age-related cardiac diseases?
What is the dominant risk factor for development of CVD?
As is shown by this study of Lakatta, aging is associated with increased left ventricular hypertrophy, increase heart failure and increased atrial fibrillation. Due to time limitation, in this lecture, I will focus only on heart failure and in the lecture in the afternoon I will focus on atrial fibrillation
Heart failure: HFrEF vs HFpEF
HFrEF = heart failure reduced ejection fraction
- enlarged left ventricle
- reduced pumping ability
- thinned walls
- weakened muscle
- ejection fraction <40%
- HFpEF = heart failure preserved ejection fraction
- normal or small left ventricle size
- high pressure needed to fill the ventricle
- thickened walls
- stiff muscle
- normal pumping capacity
- ejection fraction > 50%/40%
- normal heart
- ejection fraction >50%
What are the facts and challenges of HFpEF [a disease of cardiac ageing]
- Also called diastolic HF
- Increased with population ageing
- Leading cause of hospitalisation in the elderly
- compared with HFrEF, no evidence-based therapies for HFpEF
- HFrEF medications (e.g., neurohormonal antagonists) failed to improve mortality in patients with HFpEF
- Heterogeneous nature of the disease, which is increasingly recognised as an age-related systemic syndrome
- anti-ageing therapies that may target common HFpEF abnormalities are worth considering
Yes/No is diastolic dysfunction the same as diastolic HF (HFpEF)?
HFpEF is more severe
Autophagy is regulated by molecular pathways of longevity learned form calorie restriction, what are these longevity pathways?
- Mammalian target of rapamycin (mTOR) pathway
- Growth Hormone / IGF-1 pathway/AKT pathway
- Sirtuins
- AMP-Activated protein kinase (AMPK)
red: inhibition
green: activation
Which interventions are done that induce autophagy and delay cardiac ageing?
- life-style modifications
- caloric restriction mimetics
- transgenic activation
interventions that induce or activate autophagy could delay cardiac ageing and promote longevity. These interventions include: life stype modifications, such as caloric restriction or intermittent fasting and exercise. However, these are sometimes difficult for people to adhere. The caloric restriction mimetics would be easier for the adherence. These include spermidine, trehalose rapamycin ect. In animals, transgenic activation of certain regulators of the longevity pathway such as SIR1 can activate autophagy and reduce cardiovascaular aging.
Of the three pathways, the caloric restriction mimetics are highly interesting and high potential for therapeutic interventions.
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