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Block 3: Pathophysiology and pharmacology > Ageing > Flashcards

Ageing Flashcards

1
Q

What is ageing?

A

Gradual decline of normal physiological functions in a time-dependent manner.
Leads to impaired function, decreased ability to cope with stressors, increased incidence of age-related conditions and increased vulnerability to death.

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2
Q

What is the link between ageing and disease?

A

Shift from acute to chronic (non-communicable) disease
Chronic conditions require persistent and long-term management
Increased co-morbidities requires more training and investment for dealing with complex needs

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3
Q

What is the difference between life expectancy and healthspan?

A

Life expectancy = average length of time an organism is expected to live
Healthspan = percentage of individuals life during which there are generally in good health

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4
Q

What are the hallmarks of ageing defined?

A
  1. Should manifest during normal ageing
  2. Experimental aggravation should accelerate ageing
  3. Experimental improvement should slow down ageing
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5
Q

What are the 3 groups of cellular hallmarks of ageing?

A 
Primary hallmarks (those causing damage) 
Antagonistic hallmarks (response to damage) 
Integrative hallmarks (physiological changes - link to phenotype of ageing)
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6
Q

What are the 4 primary cellular hallmarks of ageing?

A
  1. Genomic instability (increased damage/ mutations with no repair)
  2. Telomere attrition (no replication)
  3. Epigenetic alteration (loss of translation/ transcription)
  4. Loss of proteostasis (misfolding/ structural changes)
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7
Q

What are the 3 antagonistic cellular hallmarks of ageing?

A
  1. Mitochondrial dysfunction (no energy)
  2. Deregulated nutrient sensing (reducing nutrient uptake to reduce overload to damaged cells)
  3. Cellular senescence (frozen in time)
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8
Q

What are the 2 integrative cellular hallmarks of ageing?

A
  1. Stem cell exhaustion (no new cells)

2. Altered communication (no coordination)

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9
Q

In what ways can genomic instability occur?

A
  1. Changes in genetic code

2. Structural changes that lead to genome instability such as changes in lamins

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10
Q

What are lamins?

A

Proteins providing structural function and transcriptional regulation in the cell nucleus.
Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope.
Provide scaffold for chromatin and protein complexes that regulate genomic stability.

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11
Q

What is the free radical theory of ageing?

A

Ageing caused by accumulation of damage inflicted by Reactive Oxygen Species (ROS)

[Evidence against theory in study in rats where anti-oxidant gene knockout had no impact on lifespan]

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12
Q

What are Reactive Oxygen Species (ROS) molecules?

A

Highly reactive molecules with the ability to oxidise cell structures causing cell damage, lipid preoxidation and protein modification that can harm the cell integrity

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13
Q

What are telomeres?

A

Repetitive nucleotide sequences at the end of chromosomes that play a role in protecting the end of the chromosome from decay and fusion with other chromosomes

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14
Q

What is proteostasis?

A

Protein homeostasis - process by which cells control the abundance and folding of the proteome

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15
Q

What occurs in loss of proteostasis due to ageing?

A

Load can overwhelm protein quality control (PQC) systems resulting in accumulation of misfolded proteins and loss of protein homeostasis.
Age-associated diseases such as Alzheimer’s and Parkinson’s characterised by aggregations of non-native proteins

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16
Q

What is cellular senescence?

A

Formation of senescent cells in response to various stressors

[Senescent cells = cells that cease to divide]

17
Q

What is the purpose of normal cellular senescence?

A

To prevent progress of damaged cells and to trigger their removal

18
Q

How is cellular senescence affected with ageing?

A

Accumulation of senescent cells due to decreased clearance/ exhausted regenerative capacity

19
Q

What is the stem cell theory of ageing?

A

Inability of stem (or progenitor) cells to replenish the tissues of an organism,
Can be caused due to stem cell senescence or excessive proliferation leading to stem cell exhaustion and premature ageing.

20
Q

What happens to the CNS with ageing?

A

Decline in brain mass
Fewer synaptic contacts and nerve cells
Reduced cerebral blood flow
Altered NTs (e.g. decreased dopamine, 5HT and ACh)
Increased lens rigidity/ lens opacification
Slowed reaction times

21
Q

What clinical consequences are related to CNS changes with ageing?

A 
Presbyopia (long-sightedness) 
Cataract
Muscle weakness/ atrophy 
Increased risk of falls 
Increased risk of delirium
22
Q

What happens to the respiratory system with ageing?

A

Reduced lung elasticity and alveolar support
Increased chest wall rigidity
Increased V/Q mismatch
Reduced cough and ciliary action

23
Q

What are the clinical consequences of respiratory system changes with ageing?

A

Reduced vital capacity and peak expiratory flow
Increased residual volume
Reduced arterial oxygen saturation
Increased risk of infection

24
Q

What happens to the cardiovascular system with ageing?

A

Reduced maximum HR
Dilatation of aorta
Reduced number of pacing myocytes in the SAN

25
Q

What are the clinical consequences of cardiovascular system changes with ageing?

A

Reduced exercise tolerance
Widened aortic arch on X-ray
Widened pulse pressure
Increased risk of postural hypotension and AF

26
Q

What changes can occur to the endocrine system with ageing?

A

Determination in pancreatic beta-cell function

27
Q

What are the clinical consequences of endocrine system changes with ageing?

A

Increased risk of impaired glucose tolerance

28
Q

What changes can occur to the renal system with ageing?

A

Loss of nephrons
Reduced glomerular filtration rate
Reduced tubular function

29
Q

What are the clinical consequences of renal system changes with ageing?

A

Impaired fluid balance
Increased risk of dehydration/ overload
Impaired drug metabolism and excretion

30
Q

What changes can occur to the gastrointestinal system with ageing?

A

Reduced motility

31
Q

What are the clinical consequences of GI system changes with ageing?

A

Increased risk of constipation

32
Q

What changes can occur to bones and muscles with ageing?

A

Reduced bone mineral density

Loss of skeletal muscle mass and strength

33
Q

What are the clinical consequences of changes to the bones and muscles with ageing?

A

Increased risk of osteoporosis

Sarcopenia (loss of muscle mass)

Block 3: Pathophysiology and pharmacology (16 decks)

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