Aging Flashcards
What are the 5 major theories of aging?
Cellular clock Death genes DNA damage (telomere theory) Free radicals Mitochondrial damage
What are the features of the cellular clock theory of aging?
After a certain passage of time or number of cell divisions, results in death of cell line
What are the features of the death gene theory of aging?
There are certain genes (death genes) that turn on later in life (or earlier!) causing cells to deteriorate and die
What are the features of the DNA damage (telomere) theory of aging?
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.
What are the features of the free radical theory of aging?
DNA in somatic cells susceptible to attack by free radicals, leading to somatic mutations, leads to cellular dysfunction and cell death.
What are the features of the mitochondrial damage theory of aging?
Mitochondrial DNA more sensitive to free radicals? Results in loss of proteins critical to mitochondrial function, loss of energy production, leads to cell death
What are the major changes associated with aging?
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
What harmful agents can increase the rate of aging?
Smoking Radiation Free radicals Poor diet Lack of exercise
What are the effects of aging on the heart?
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
What are the consequences of aging on the heart?
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
What causes hypertrophy of the left ventricle?
Results from:
Decrease in arterial elasticity (caused by increased stiffness of aorta )
- causes increases in aortic pressure which increases cardiac work
What are the different types of cardiac hypertrophy that occur with aging?
Concentric hypertrophy
Eccentric hypertrophy
Describe concentric hypertrophy
Increased diameter of cardiomyocytes
Increased ventricular wall thickness
Can reduce chamber size
Describe eccentric hypertophy
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
Why do you develop a gradual decrease in maximum heart rate?
Conduction System:
- Decrease in the number of SA node cells
-
By how much does heart rate decrease with age?
Decreased resting and maximum cardiac output by 30-60% by age of 85 years
How does the connective tissue in the heart valves change with age?
Less flexible and Ca2+ deposits increase
Abnormal function
- May become either stenosed or incompetent
How does the control of blood pressure change with age?
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
What is the end result of aging on the heart?
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
How is the respiratory system affected by aging?
Almost all aspects of the respiratory system are affected by aging:
- Structural
- Physiological
- Immunological
What is compliance?
Change in volume relative to change in pressure
What does compliance determine?
Lung compliance determines rate and force of expiration
Thoracic compliance determines elastic load during inspiration
What are the effects of aging on the respiratory system?
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
Why does lung compliance gradually increase with age?
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
Why can you get decreased lung compliance with age?
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
What structural changes to the thoracic cage occur with age?
Osteoporosis (reduce height of vertebrae)
Calcification of rib cage (stiffening)
Kyphosis
What is the result of decreased chest wall compliance?
Less expansion on inspiration
Diaphragm less effective at contracting
Why does the diaphragm lose strength with age?
Diaphragm less strong due to atrophy
What is the result of the increased diameter of alveolar ducts and bronchioles?
Increased dead space
Decrease in the amount of air available for gas exchange (alveolar ventilation)
What is the result of decreased diffusion capacity?
Decreased alveolar surface area and increased thickness
Decreased pulmonary capillary blood flow
How does the body compensate for increased alveolar duct and bronchiole diameter, and decreased diffusion capacity?
Gradual increase in tidal volume
What changes in respiratory test results occur?
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
What are the changes in respiratory tests due to?
Weakening of respiratory muscles
Decreased compliance of the thoracic cage caused by stiffening of cartilage and ribs
Why does mucus accumulation increase with age?
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
How is respiratory gas exchange affected by aging?
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
What immune changes in the respiratory system occur with age?
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
What changes in control of ventilation occur with age?
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
