Ageing Flashcards
What is ageing?
The loss with time of the organisms adaptability to internal and external stresses (e.g. loss of homeostatic mechanism) whether it is a cell, organ or whole body
What do 4 criteria do factors going wrong in ageing need to be:
- intrinsic to all cells
- deleterious
- progressive
- universal to species
Who do we often study to look at ageing?
- people over 100 y/o
- people with premature ageing
What factors cause ageing at the cellular level?
- Oxidative stress
- Calorie intake
What is cellular ageing associated with>
- Damage to DNA and loss of gene function
- Degeneration of cellular organelles
- Shortening of telomeres
What is oxidative stress?
Radicals produced by normal metabolism take electrons from other parts of the cell = damage to DNA, fatty acids and membranes = disrupts normal signalling processes
What anti-oxidants do we naturally produce?
Provitamin A and vitamins C and D
What does a cell produce when its under stress?
Cellular stress proteins e.g. heat stress protein (hip) 60, 70 and 90 = protect proteins and degrade/repair damaged protein
What is the impact of calorie impact on longevity?
Decreased calories means living longer -> possibly due to increased oxidative stress, decreased insulin and activation of sirtuins
What are sirtuins?
Family of enzymes found within many cells thought to be involved in maintaining healthy life within the cell (regulate transcription, apoptosis and stress)
What are telomeres?
Part of essential, non coding DNA preventing the ends of chromosomes joining together, up to 2000 repeats of TTAGGG, n.b. there is partial loss during each round of cell division (repetitive senescence = loss of whole thing in 125 duplications), some evidence that telomeres can increase in length in response to healthy lifestyle changes
What are the two ageing theories?
- Wear and tear theory
2. Mis-repair theory
What is the wear and tear theory?
Damage accumulates, and is a by-product of metabolism, we are unable to repair random environmental damage
What is the mis-repair theory?
Cells repair serious or repeated damage, errors accumulate with age and gradually cause disorganisation within a tissue
Why do some people age faster than others?
25% ageing is genetically controlled (repair mechanisms, determine basal metabolic rate -> lower associated with increased longevity) but also controlled by environment, nutrition and lifestyle
What is the effect of ageing on the immune system?
Less response to outside antigens (infection), heightened response to own antigens (autoimmunity -> arthritis, glomerular nephritis, endocrine disorders e.g. hypo and hyperthyroidism) and general decline in T cell function, may contribute to cancer
What is the effect of ageing on the brain?
Reduced brain plasticity via biochemical changes rather than neuronal loss = decreased brain mass, neuronal loss with proliferation of glia, decrease in connectivity and neurotransmitter function, increased incidence of infarcts, stroke, number of senile plaques and neurofibrillary tangles (significant mental decay after 75 y/o in both male and female)
What is the effect of ageing on taste?
Taste thresholds increase (loss of receptor cells in taste buds) -> add more salt to food
What is the effect of ageing on smell?
Loss of olfactory cells so loss
What is the effect of viral infections, medications and radiation on taste and smell?
Make underlying ageing process worse and can be sudden onset
How does age affect metabolism?
It declines (less energy produced)
How does age affect physical plasticity of tissue?
It declines (more cross links between collagen molecules = more tissue rigidity and loss in some tissues)
How does age effect functional reserve of organs?
It declines = less able to deal with insult = signs of frailty, disability and disease
How does age effect vulnerability to stress and infection?
It increases
How is the ageing population affecting dentition?
More dentate >65
21 teeth = critical number for function dentition
More tooth wear
How does oral health related to dental health in the ageing population?
- Aspiration pneumonia
- Periodontal disease and diabetes
- Periodontal disease, cardiovascular disease and stroke
- Pain and discomfort
- Low self esteem
- Reduced social interactions
- Reduced enjoyment of life
To age successfully you should (7):
- Don’t smoke
- Exercise
- Watch your weight
- Manage stress well
- Do not abuse alcohol
- Enjoy stable marriage
- Look after your teeth
What is intrinsic ageing?
Genetic ageing = continuous process and begins in mid 20s
What is extrinsic ageing?
Caused by environmental factors e.g. Sun exposure and smoking = premature ageing
What is the consequence of ageing on skin? (7)
- compromised skin function especially after injury (delayed recovery of barrier function)
- decreased cytokine production
- decreased fibre synthesis
- decreased vit d production
- changes in blood vessel wall architecture
- decreased sweat and sebum production
- DNA repair rate decreases (correlates inversely with mutation risk, accumulation of oxidation damage and skin cancer susceptibility)
What are the signs of skin ageing?
- fine wrinkles
- thin transparent skin
- loss of underlying fat
- sagging
- dry skin that may itch
- inability to sweat efficiently
What is the histological outcome of ageing of skin?
- flattening of dermal-epidermal interface
- progressive decrease in melanocytes and langerhans cells
- dermis loses ECM
- increased MMPs (matrix metalloproteinases) and decreased TIMPs (tissue inhibitors of matrix metalloproteinases) = imbalanced collagen turnover (lose more than gain)
- loss of fibroblasts
- loss of vascular networks
- decrease in signalling pathways concerned with protein phosphorylation
What does the degree of photo ageing depend upon?
History of long term or intense exposure to UV light
What are the histological aspects of photo ageing?
- dermal elastosis (deposition of abnormal elastic material)
- collagen and elastic fibres show degenerative changes
- variable thickness in epidermis with organisation of cells and presence of atypical cells
- inflammatory cells in dermis
What is the effect of age on muscle?
- loss of size and strength
- begins in 4th decade of life (1% lean muscle lost per year after the age of 40)
- decreased in synthesis of many muscle proteins (myosin, mitochondrial
- muscle weakness
- reduced endurance capacity
- insulin resistance
- water content of tendons decreases = muscles become stiffer and less able to tolerate stress
- M>F
- decreased muscle protein turnover
- decreased ATP may signal hypothalamus to reduce spontaneous physical activity
- change in capacity of m
- affected by diet and exercise (damage may be reversible by exercise)
What happens in bone with ageing?
- bone structure constantly remodelling = repair and changing functional requirements
- generalised thinning of cortical bone
- increased trabecular spacing
- increased dead osteocytes (live 35 yrs) -> become mineralised = sclerotic and more brittle bone
- reduce cellularity and vascularity = poor healing
Does osteoporosis affect the jaws?
Controversial, a lot of evidence suggesting it is and a lot suggesting it’s not!
Human studies: positive correlation between osteoporosis and low mineral density in mandible, visible changes in mandibular cortex on radiographs, severity of residual ridge resorption and large number of missing teeth
Animal studies: increased radiolucency after oestrogen deficient, principally high bone resoprtive activity, occlusal hypo function further increased this and micro structural damage in monkey alveolar bone connected
What happens in the salivary glands with age?
It’s thought that undergoes anatomical changes, parotid gland is less susceptible to tissue changes and has no reduction in function
Some studies showed salivary production remained stable in healthy adults despite loss of acinar cells
- reduction in rate of secretory proteins synthesis and mucins decreased
- lymphocytic infiltration
- less secretory vesicles
Describe xerostomia:
Dry mouth = pathological
= difficulties with mastication swallowing tasting and speech and discomfort esp for denture wearers
- often associated with medication, Sjögren’s syndrome and irradiation of head and neck
- increased risk of caries and periodontal disease and oral infections e.g. C. Albicans
What factor was found to decrease in salivary glands with age in the senescence accelerated mouse model?
Insulin like growth factor 1 (IGF-1)
What are the different types of oral mucosa?
Masticatory, lining and specialised
What is the effect of ageing thought to be on oral mucosa?
- more fragile, less well keratinised m, thinner epithelium
- changes in collagen and elastin fibres (weakens mucosa)
- wound healing impaired
- loses elasticity and becomes more inflexible
- fordyce spots increase (yellow spots on Buccal mucosa)
- minor salivary glands decrease
How does the tongue age?
- thinning of epithelium on dorsal and lateral aspect
- less interdigitation between epithelium and lamina propria
- collagen content increases (fibrosis)
- decrease in number of taste fibres but not taste buds
How does the gingiva age?
- Recession increases (could be secondary)
- little change in epithelium reported (some increase in collagen content of lamina propria)
What happens to mucosal lesions with age?
- greater susceptibility and prevalence (fragile, salivary gland decreased antibodies)
- raised level of p53 (DNA repair)
How does enamel age?
- increased pigmentation
- increased attrition, abrasion and erosion
- increased trace elements
- mineralisation of outer surface = decreased permeability
How does dentine age?
Intratubular dentine = sclerotic and translucent dentine (filling in of tubules)
How does the pulp age?
- decrease in size
- decreased cellular elements
- increased fibrous tissue
- increased calcifications
- decreased vascularity and sensitivity
How does cementum age?
- Increase in amount (3 fold from 16-70)
- salter lines = periodicity
- repair/ cementicles/ areas of resorption
How does the PDL age?
- poor understanding
- less mobile with age (ankylosis)
- Periodontal space narrows slightly
- PDL thickness often unchanged
- decreased cellularity and mitotic index reported
- fat cells appearing within PDL
What do aged periodontal fibroblasts show?
- decreased ER area
- decreased area occupied by collagens
- decreased number and increased side of intercellular contacts
- decreased protein synthesis and collagen degradative properties
- express cytokeratin 19 and vimentin
What happens to the ECN of the PDL with age?
- changes in collagen fibres and ground substance
- increased collagen fibrosis or decrease in number of collagen fibres and rate of collagen synthesis with age
- slowing down of healing
