Aging

Question 1

What are the 5 major theories of aging?

Answer 1

Cellular clock
Death genes
DNA damage (telomere theory)
Free radicals
Mitochondrial damage

Question 2

What are the features of the cellular clock theory of aging?

Answer 2

After a certain passage of time or number of cell divisions, results in death of cell line

Question 3

What are the features of the death gene theory of aging?

Answer 3

There are certain genes (death genes) that turn on later in life (or earlier!) causing cells to deteriorate and die

Question 4

What are the features of the DNA damage (telomere) theory of aging?

Answer 4

DNA damage causes cell degeneration and death.

Telomere theory

• DNA protected from damage by a specific sequence of nucleotides (TTAGGG) at the end of chromosomes.
• Role is to protect the end of the chromosome during mitosis
• Telomeres therefore take the brunt of this replicative loss and protect regions of DNA that code for essential proteins.

Telomerase: repairs and maintains integrity of the telomere
- absent in aging populations of somatic cells.

Question 5

What are the features of the free radical theory of aging?

Answer 5

DNA in somatic cells susceptible to attack by free radicals, leading to somatic mutations, leads to cellular dysfunction and cell death.

Question 6

What are the features of the mitochondrial damage theory of aging?

Answer 6

Mitochondrial DNA more sensitive to free radicals? Results in loss of proteins critical to mitochondrial function, loss of energy production, leads to cell death

Question 7

What are the major changes associated with aging?

Answer 7

Many cells proliferate throughout life

Some cease to proliferate once they reach a certain number, dead cells are not replaced
- Neuronal loss, rate declines as we get older

Muscle cells (don’t proliferate)

• Number of skeletal and cardiac muscle fibres declines
• Weaker (reverse with exercise)

Physical plasticity

• Increase collagen and increased cross linking with age
• Rigid and less elastic
• Lens of eye has high levels of collagen, as such one of the first structures to exhibit changes

Immune system

• Less response to antigens
• More sensitive to own antigens (autoimmunity)
• Arthritis, glomerular nephritis, hyperthyroidism

Question 8

What harmful agents can increase the rate of aging?

Answer 8

Smoking
Radiation
Free radicals
Poor diet
Lack of exercise

Question 9

What are the effects of aging on the heart?

Answer 9

Gradual changes in function

• Minor under resting conditions
  - Homeostatic mechanisms compensate
• More significant in response to exercise

Age-related diseases develop
E.g. atherosclerosis, LV hypertrophy

Progressive deposition of collagen (fibrosis)

• in the vascular wall
• in the cardiac interstitial and perivascular space
• increased myocardial and arterial stiffness
• impaired relaxation -> diastolic dysfunction

Question 10

What are the consequences of aging on the heart?

Answer 10

Hypertrophy of the left ventricle
Gradual decrease in maximum heart rate
Altered electrical conduction system of the heart
Decreased HR response to Adr & NorAdr
Longer contraction and relaxation times for cardiac muscle
Decreased resting and maximum cardiac output
Changes in connective tissue of heart valves
Impaired ability to buffer changes in BP

Question 11

What causes hypertrophy of the left ventricle?

Answer 11

Results from:
Decrease in arterial elasticity (caused by increased stiffness of aorta )
- causes increases in aortic pressure which increases cardiac work

Question 12

What are the different types of cardiac hypertrophy that occur with aging?

Answer 12

Concentric hypertrophy

Eccentric hypertrophy

Question 13

Describe concentric hypertrophy

Answer 13

Increased diameter of cardiomyocytes
Increased ventricular wall thickness
Can reduce chamber size

Question 14

Describe eccentric hypertophy

Answer 14

Lengthening of myocytes
Thin, long left ventricular walls
Increased volume of left ventricle
Increases left atrial pressure & pulmonary capillary pressure

Causes pulmonary oedema
- breathlessness during exercise

Question 15

Why do you develop a gradual decrease in maximum heart rate?

Answer 15

Conduction System:
- Decrease in the number of SA node cells
-

Question 16

By how much does heart rate decrease with age?

Answer 16

Decreased resting and maximum cardiac output by 30-60% by age of 85 years

Question 17

How does the connective tissue in the heart valves change with age?

Answer 17

Less flexible and Ca2+ deposits increase

Abnormal function
- May become either stenosed or incompetent

Question 18

How does the control of blood pressure change with age?

Answer 18

Impaired ability to buffer changes in BP

This may be due to the reduced sensitivity of the cardiovagal baroreflex (i.e. blunted reflex changes in R-R interval in response to a change in BP)

• Arterial stiffening (aorta and carotid artery)
• Decreased response to Ach
• Neural deficit in the baroreflex arc

Question 19

What is the end result of aging on the heart?

Answer 19

The enlarged and thickened cardiac muscle, especially in the left ventricle, consumes more oxygen to pump the same amount of blood pumped by a younger heart

This change is not significant except if the coronary circulation is decreased by coronary artery disease

Question 20

How is the respiratory system affected by aging?

Answer 20

Almost all aspects of the respiratory system are affected by aging:

• Structural
• Physiological
• Immunological

Question 21

What is compliance?

Answer 21

Change in volume relative to change in pressure

Question 22

What does compliance determine?

Answer 22

Lung compliance determines rate and force of expiration

Thoracic compliance determines elastic load during inspiration

Question 23

What are the effects of aging on the respiratory system?

Answer 23

Structural changes to thoracic cage
Decreased chest wall compliance
Diaphragm also less strong due to atrophy
Lung compliance gradually increases with age
Exhalation becomes more difficult due to increased residual volume

Question 24

Why does lung compliance gradually increase with age?

Answer 24

Lung distends easily but with decreased elastic recoil

Due to progressive deterioration and enlargement of alveoli (senile emphysema)
- Lung parenchyma loses its supporting structure causing dilation of air spaces

Question 25

Why can you get decreased lung compliance with age?

Answer 25

The reduction in chest wall compliance is slightly greater than the increase in lung compliance, resulting in an overall moderate decline in total compliance of the respiratory system

Question 26

What structural changes to the thoracic cage occur with age?

Answer 26

Osteoporosis (reduce height of vertebrae)
Calcification of rib cage (stiffening)
Kyphosis

Question 27

What is the result of decreased chest wall compliance?

Answer 27

Less expansion on inspiration

Diaphragm less effective at contracting

Question 28

Why does the diaphragm lose strength with age?

Answer 28

Diaphragm less strong due to atrophy

Question 29

What is the result of the increased diameter of alveolar ducts and bronchioles?

Answer 29

Increased dead space

Decrease in the amount of air available for gas ex­change (alveolar ventilation)

Question 30

What is the result of decreased diffusion capacity?

Answer 30

Decreased alveolar surface area and increased thickness

Decreased pulmonary capillary blood flow

Question 31

How does the body compensate for increased alveolar duct and bronchiole diameter, and decreased diffusion capacity?

Answer 31

Gradual increase in tidal volume

Question 32

What changes in respiratory test results occur?

Answer 32

Decreased vital capacity

• Decreased ability to fill the lungs (decreased inspiratory reserve volume)
• Decreased ability to empty the lungs (decreased expiratory reserve vol­ume)

Decreased maximum minute ventilation rates
Decreased exercise capacity

Question 33

What are the changes in respiratory tests due to?

Answer 33

Weakening of respiratory muscles

Decreased compliance of the thoracic cage caused by stiffening of carti­lage and ribs

Question 34

Why does mucus accumulation increase with age?

Answer 34

Mucus-cilia escalator is less able to move the mucus because it becomes more viscous and because the number of cilia and their rate of movement decrease

As a consequence, the elderly are more susceptible to respiratory infections and bronchitis

Question 35

How is respiratory gas exchange affected by aging?

Answer 35

Decreased gas exchange across the res­piratory membrane as parts of alveolar walls lost

Reduction in the surface area available for gas exchange, and the remaining walls thicken, which decreases diffusion of gases

A gradual increase in resting tidal volume with age compensates for these changes

Question 36

What immune changes in the respiratory system occur with age?

Answer 36

Increased number of neutrophils
Decrease in macrophages
- but produce more free radicals in response to stimuli

Epithelial lining fluid

• rich in antioxidants
• minimises oxidative injury to the respiratory epithelium following toxic exposure
• Exposure over time causes changes in composition

Question 37

What changes in control of ventilation occur with age?

Answer 37

The ventilatory response to both hypoxia and hypercapnia diminishes with age

This may be due to the reduced sensitivity of the central and peripheral chemoreceptors