Ageing Flashcards
What is ageing?
A distinct and progressive decline in function which makes us more vulnerable to disease
Common processes seen in most ageing tissues:
- 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
Examples of functional decline as we age?
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
Body composition and homeostasis as we age?
- 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
Slide 6
Conclusions of the study titled “Effect of aging and physical activity on left ventricular compliance”?
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.)
Conclusions of the study titled “Refining patterns of left ventricular hypertrophy using cardiac MRI”?
“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.”
Effect of ageing on pulmonary?
- Decreased elastic recoil, airways collapse earlier
- Decreased forced vital capacity, functional residual capacity, residual volume, FEV1
- Decreased ventilatory response and chemoreceptor function
Affect of Decreased elastic recoil, airways collapse earlier?
Increases residual volume
Affect of Decreased forced vital capacity, functional residual capacity, residual volume, FEV1??
Can’t expel CO2 so efficiently
Affect of Decreased ventilatory response and chemoreceptor function?
Increased hypoxia and hypercapnia
How is renal affected by ageing?
- 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
How is endocrine system affected by ageing?
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.)
Affect of ageing on immunosenescence?
- Decreased T-helper cell activity (CD4+)
- Increased Killer T-cell activity (CD8+)
- Decreased Ab response to foreign antigen
- Increased auto-antibodies
Conclusions of the study titled “Mechanisms of immunosenescence”?
“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.”
Other Clinical Features of Normal Ageing?
- 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
A theories around ageing fall into 1 of 3 groups which are:
1) Biological clock
2) Non-reversible cellular changes
3) Cellular damage
Monozygotic twins have life spans that are …
…closer than dizyotic twins
Each species has its own …
… average longevity
Ageing is programmed into…
…each species
The most popular theory of ageing concerns …
…telomere shortening (mitotic division counter)
- Somatic cells have a limited number of divisions
Somatic cells have a limited number of…
…divisions
Slide 20
The limit was found to correlate with …
…telomere length – the more times a cell had replicated, the shorter its telomere
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
What might happen to red and white blood cell production because of hayflick limit?
Red and white blood cell production slows
What might happen to immune system because of hayflick limit?
Immune system less responsive
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)
Affect of hayflick limit on the epithelium?
- Know that skin gets thinner as we age
- The GI tract becomes leaky
We can’t stop these cells dividing, but we can …
…slow the need for their replacement
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
Overtime, spontaneous reactions cause …
…cross-linking between proteins and other molecules
Overtime, spontaneous reactions cause cross-linking between proteins and other molecules
These proteins are …
…irreversibly altered
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
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
Commonly affected body proteins by cross-linkage theory?
Enzymes, Collagen, Elastin, Lens proteins
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
Because of cross-linkage theory, the skin becomes…
…less elastic
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
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
What are free radicals?
Atoms or groups of atoms possessing one or more unpaired electrons
Where are free radicals produced?
- Mitochondria
- Endothelial cells
- Immune cells
In mitochondria, the free radical contains…
…oxygen – thus often termed a reactive oxygen species (ROS)
Any thing that promotes ROS production can also cause …
…cross linking
- Any thing that promotes ROS production can also cause cross linking
- A good example is…
… the skin.
- 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
Cross linked skin = ?
Cross linked skin = leather
Excessive alcohol can also cause…
…cross linked skin.
Acetaldehyde, one of the products of alcohol dehydrogenase has…
…powerful cross-linking activity
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.
Cross linking of skin (and other tissues) is promoted by…
…any lifestyle choice that promotes the production of ROS
Antioxidants can help
But sometime the lifestyle choice and a poor diet leads to …
…antioxidant depletion
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.”
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..”
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
In general, with age, pathways initiating repair …
…decrease and pathways initiating apoptosis increase in activity
Cross linking followed by apoptosis can lead to…
…extracellular rubbish.
Cross linked material often …
… resists degradation
Accumulation both intra and extra-cellularly can lead to …
…cell, tissue & organ dysfunction and death
- 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
What is lipofuscin?
Yellow-brown pigments, inert, strongly cross-linked.
What is lipofuscin formed from?
Lipids
Lipofuscin is a major pigment of …
…spots and earwax
Extracellular junk/rubbish accumulates in many…
…organs such as heart, eyes and brain
Other cellular junk include…
…amyloid - cross
Over time long lived cells accumulate …
… lipofuscin.
Over time long lived cells accumulate lipofuscin and other…
…highly cross-linked organic substances such as amyloid & ceroid.
Over time long lived cells accumulate lipofuscin and other highly cross-linked organic substances such as amyloid & ceroid.
This interferes with …
…normal cellular recycling
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.
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
Long lived cells include …
…cardiac myocytes, neurons and retinal pigment epithelial cells
Examples of lipofuscin associated disease?
- RPE
- Macular degeneration
- Neurons
- Parkinson’s disease
- Cardiac myocytes
- Brown atrophy
No one theory explains …
…growing old
Program theories help understand …
…differences in ageing between species
Gene-based theories help understand …
…differences between individuals within a species.
BUT, individuals vary in terms of …
…diseases, experiences, lifestyles, mutations, errors, and accumulations. Therefore, individuals age at different rates and in different ways.
