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Ageing Flashcards

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1
Q

What is ageing?

A

A distinct and progressive decline in function which makes us more vulnerable to disease

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2
Q

Common processes seen in most ageing tissues:

A
  • Decrease in amount of tissue
  • Altered molecular composition
  • Accumulation of degraded molecules
  • Reduced efficiency of functional elements
  • Reduced synthetic capacity of differentiated cells
  • Decline in stem cells
  • Altered levels of hormones, growth factors and cytokines or altered ability of cells to respond to them
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3
Q

Examples of functional decline as we age?

A

1) Cognitive functions
- Normal decline
- Increase risk of Dementia
2) Senses
- Visual: eyesight deteriorates
- Auditory: Poorer hearing
- Balance: Increased risk of falls
3) Continence
- Front and back

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4
Q

Body composition and homeostasis as we age?

A
  • Decrease muscle mass
  • Increase body fat
  • Decrease in % water
  • Changes volume of distribution
  • Increased bone loss
  • Impaired baroreceptor function
    – Orthostatic hypotension
    – Dizziness due to when a person’s blood pressure suddenly falls when they stands up
  • Impaired thermoregulation
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5
Q

Slide 6

A
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6
Q

Conclusions of the study titled “Effect of aging and physical activity on left ventricular compliance”?

A

A sedentary lifestyle during healthy aging is associated with decreased left ventricular compliance, leading to diminished diastolic performance. Prolonged, sustained endurance training preserves ventricular compliance with aging and may help to prevent heart failure in the elderly. (Circulation. 2004;110:1799-1805.)

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7
Q

Conclusions of the study titled “Refining patterns of left ventricular hypertrophy using cardiac MRI”?

A

“Left ventricular hypertrophy (LVH) is generally considered to be an adaptive response that allows for normal ejection fraction despite abnormal pressure and/or volume load. However, this adaptation is associated with increased cardiac morbidity and mortality, including acute myocardial infarction, heart failure, arrhythmia, and stroke.”

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8
Q

Effect of ageing on pulmonary?

A
  • Decreased elastic recoil, airways collapse earlier
  • Decreased forced vital capacity, functional residual capacity, residual volume, FEV1
  • Decreased ventilatory response and chemoreceptor function
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9
Q

Affect of Decreased elastic recoil, airways collapse earlier?

A

Increases residual volume

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10
Q

Affect of Decreased forced vital capacity, functional residual capacity, residual volume, FEV1??

A

Can’t expel CO2 so efficiently

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11
Q

Affect of Decreased ventilatory response and chemoreceptor function?

A

Increased hypoxia and hypercapnia

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12
Q

How is renal affected by ageing?

A
  • Decreased mass and number of glomeruli
  • Increased glomerulosclerosis (Scarring of the glomeruli)
  • Glumular Filtration Rate slowly decreases
  • Decreased Na+ retention; decreased responsiveness to Arginine vasopressin (AVP)
  • Less concentration of urine
  • Decreased thirst and drink response
  • Resulting in increased dehydration
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13
Q

How is endocrine system affected by ageing?

A

1) Decreased glucose tolerance (Fasting Glucose decreases 1 mg/dL/decade) (Independent of obesity and inactivity)
2) Increased insulin resistance
3) Decreased Growth hormone (GH) & Insulin-like Growth Factor (IGF-1)
(Give elderly men GH, increases lean body mass) (IGF-1 is important for growth in children and has anabolic effects in adults.)

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14
Q

Affect of ageing on immunosenescence?

A
  • Decreased T-helper cell activity (CD4+)
  • Increased Killer T-cell activity (CD8+)
  • Decreased Ab response to foreign antigen
  • Increased auto-antibodies
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15
Q

Conclusions of the study titled “Mechanisms of immunosenescence”?

A

“Alterations to the immune system in the older person are generally viewed as a deterioration of immunity, leading to the use of the catch-all term immunosenescence. Indeed, many immunological parameters are often markedly different in elderly compared to young people, and some, mostly circumstantial, evidence suggests that retained function of both innate and acquired immunity in the elderly is correlated with health status.”

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16
Q

Other Clinical Features of Normal Ageing?

A
  • Loss of muscle mass
  • Decreased musculoskeletal mobility
  • Reduction in bone mass (osteoporosis)
  • Thinning and reduced elasticity of skin (wrinkling)
  • Slower wound repair
  • Brain, liver, kidneys – a low amount of cellular loss and reduction in mass
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17
Q

A theories around ageing fall into 1 of 3 groups which are:

A

1) Biological clock
2) Non-reversible cellular changes
3) Cellular damage

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18
Q

Monozygotic twins have life spans that are …

A

…closer than dizyotic twins

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19
Q

Each species has its own …

A

… average longevity

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20
Q

Ageing is programmed into…

A

…each species

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21
Q

The most popular theory of ageing concerns …

A

…telomere shortening (mitotic division counter)

  • Somatic cells have a limited number of divisions
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22
Q

Somatic cells have a limited number of…

A

…divisions

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23
Q

Slide 20

A
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24
Q

The limit was found to correlate with …

A

…telomere length – the more times a cell had replicated, the shorter its telomere

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25
What cells are effected by the hayflick limit?
- The cells that are continuously dividing by mitosis - Bone marrow, epithelium, fibroblast cells - We know that the rates of division does decrease with age
26
What might happen to red and white blood cell production because of hayflick limit?
Red and white blood cell production slows
27
What might happen to immune system because of hayflick limit?
Immune system less responsive
28
Link between fibroblast cells, rats and colalgen?
In rats rates of collagen synthesis decrease ten-fold between 1-24 months (8 to 60 human years)
29
Affect of hayflick limit on the epithelium?
- Know that skin gets thinner as we age - The GI tract becomes leaky
30
We can’t stop these cells dividing, but we can ...
...slow the need for their replacement
31
What can make the hayflick limit worse?
1) Obvious example is exposing the skin to ultraviolet light - Tanning - Damages cells by photo-oxidation - Cells need to be replaced encouraging division 2) Nutrition - Anything that helps protect from UV damage - Vitamin A, B-carotene etc
32
Overtime, spontaneous reactions cause ...
...cross-linking between proteins and other molecules
33
Overtime, spontaneous reactions cause cross-linking between proteins and other molecules These proteins are ...
...irreversibly altered
34
Overtime, spontaneous reactions cause cross-linking between proteins and other molecules These proteins are irreversibly altered This leads to ...
...structural changes, leading to altered protein function
35
Overtime, spontaneous reactions cause cross-linking between proteins and other molecules These proteins are irreversibly altered This leads to structural changes, leading to altered protein function May have two consequences which are...
1) Protein resists degradation 2) Long lived proteins become non-functional
36
Commonly affected body proteins by cross-linkage theory?
Enzymes, Collagen, Elastin, Lens proteins
37
Example of how cross linkage theory affects eye?
- As people age they become short-sighted - This is because the lens, a bag of proteins, becomes less flexible - Cross linking of the lens proteins is though to contibute
38
Because of cross-linkage theory, the skin becomes...
...less elastic
39
Nutritional aspects of cross linkage theory?
1) Avoid high glycaemic foods when possible (particularly highly processed) 2) Remember that the initial reaction is reversible, so a period of low blood glucose levels each day will help reverse any amadori products formed 3) Some suggestion that aspirin may block their formation 4) Some evidence that Histidine-rich proteins may also slow cataract formation
40
Link between aspirin and cross linkage theory?
1) Some suggestion that aspirin may block their formation - People who take aspirin regularly develop less cataracts - Aspirin is naturally found in stressed fruit and veg
41
What are free radicals?
Atoms or groups of atoms possessing one or more unpaired electrons
42
Where are free radicals produced?
- Mitochondria - Endothelial cells - Immune cells
43
In mitochondria, the free radical contains...
...oxygen – thus often termed a reactive oxygen species (ROS)
44
Any thing that promotes ROS production can also cause ...
...cross linking
45
- Any thing that promotes ROS production can also cause cross linking - A good example is...
... the skin.
46
- Any thing that promotes ROS production can also cause cross linking - A good example is the skin - Sunbathing (UV) can cause...
... ROS that lead to molecules in the skin cross linking
47
Cross linked skin = ?
Cross linked skin = leather
48
Excessive alcohol can also cause...
...cross linked skin.
49
Acetaldehyde, one of the products of alcohol dehydrogenase has...
...powerful cross-linking activity
50
This is the reason why alcoholics, sun-aholics and older people can develop leathery skin The skin needs ...
...a source of antioxidants to protect it from ROS (Vitamin C, Vitamin A, Beta-carotene.
51
Cross linking of skin (and other tissues) is promoted by...
...any lifestyle choice that promotes the production of ROS
52
Antioxidants can help But sometime the lifestyle choice and a poor diet leads to ...
...antioxidant depletion
53
Conclusions of the study titled "Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke"?
“The mechanisms by which exposure to cigarette smoke dramatically increase the incidence and severity of atherosclerosis and the incidence of lung cancer, chronic obstructive airways disease, and emphysema are incompletely understood. Epidemiologic evidence has suggested a modifying role for antioxidant micronutrients, including tocopherols and carotenoids, in these disease processes … We exposed freshly obtained human plasma to the gas phase of cigarette smoke to assess its effects on tocopherols, carotenoids, and retinol…We conclude that a wide spectrum of lipophilic micronutrients undergo degradation when exposed to gas-phase cigarette smoke.”
54
What were the conclusions of the study titled "Does cigarette smoking make you ugly and old?"?
“…the data are consistent with the conclusion that smoking causes skin wrinkling that could make smokers appear unattractive and prematurely old..”
55
WHat were the conclusions of the study titled "Cigarette smoking associated with premature facial wrinkling: image analysis of facial skin replicas"?
“This study suggests that attention should be paid to smoking-associated facial wrinkling (not evident from a visual assessment) in young people and added to the list of disorders seemingly caused by smoking…Because smoking-associated wrinkling is not readily apparent in the early stages, compared to photoaging, many young persons underestimate the harmful cumulative effects of smoking on the skin…Smokers need to be made aware of the increased risks of premature skin aging as a result of their smoking habit
56
In general, with age, pathways initiating repair ...
...decrease and pathways initiating apoptosis increase in activity
57
Cross linking followed by apoptosis can lead to...
...extracellular rubbish.
58
Cross linked material often ...
... resists degradation
59
Accumulation both intra and extra-cellularly can lead to ...
...cell, tissue & organ dysfunction and death
60
- Cross linked material often resists degradation - Accumulation both intra and extra-cellularly can lead to cell, tissue & organ dysfunction and death - A common example is...
...lipofuscin
61
What is lipofuscin?
Yellow-brown pigments, inert, strongly cross-linked.
62
What is lipofuscin formed from?
Lipids
63
Lipofuscin is a major pigment of ...
...spots and earwax
64
Extracellular junk/rubbish accumulates in many...
...organs such as heart, eyes and brain
65
Other cellular junk include...
...amyloid - cross
66
Over time long lived cells accumulate ...
... lipofuscin.
67
Over time long lived cells accumulate lipofuscin and other...
...highly cross-linked organic substances such as amyloid & ceroid.
68
Over time long lived cells accumulate lipofuscin and other highly cross-linked organic substances such as amyloid & ceroid. This interferes with ...
...normal cellular recycling
69
Over time long lived cells accumulate lipofuscin and other highly cross-linked organic substances such as amyloid & ceroid. This interferes with normal cellular recycling Consequently...
...damaged mitochondria accumulate in these cells increasing ROS production.
70
Over time long lived cells accumulate lipofuscin and other highly cross-linked organic substances such as amyloid & ceroid. This interferes with normal cellular recycling Consequently, damaged mitochondria accumulate in these cells increasing ROS production. This reduces...
...the efficiency of the cell, eventually triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death
71
Long lived cells include ...
...cardiac myocytes, neurons and retinal pigment epithelial cells
72
Examples of lipofuscin associated disease?
- RPE - Macular degeneration - Neurons - Parkinson’s disease - Cardiac myocytes - Brown atrophy
73
No one theory explains ...
...growing old
74
Program theories help understand ...
...differences in ageing between species
75
Gene-based theories help understand ...
...differences between individuals within a species.
76
BUT, individuals vary in terms of ...
...diseases, experiences, lifestyles, mutations, errors, and accumulations. Therefore, individuals age at different rates and in different ways.

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