A- Ageing Flashcards
What is Ageing (biological)?
‘Complex biological process in which changes at the molecular, cellular and organ levels results in a progressive inevitable and inescapable decrease in the body’s ability to respond appropriately to internal and/or external stressors’
Characteristics of ageing
Increased mortality
Increased susceptibility & vulnerability to disease
e.g. >65 years, 92 times more likely to get heart disease
Changes in biochemical composition of tissues
Increased protein crosslinking, aberrant folding, lipofuscin accumulaton
Decrease in physiological capacity
e.g. reduced glomerular filtration rate, max. heart rate
Reduced ability to respond to environmental stimuli
Old Theories of ageing (3)
> Galen (AD129- 199)
Changes in body humours beginning in early life
Slow increase in dryness & coldness of the body
> Roger Bacon (1220-1292)
Wear & tear theory
Result of abuses & insults to the body
Good hygiene may slow process
> Charles Darwin (1809-1892)
Loss of irritability in nervous & muscular tissue
Programmed theories of ageing
- Biological clocks
- Purposeful programme driven by genes
e.g. Evolutionary
Non programmed (error, stochastic) theories of ageing
- Progressive random, accidental damage
- Loss of molecular fidelity
e. g. Molecular/cellular
e. g. System
Evolutionary theory of ageing
Genome directs life until sexual maturity.
No selective pressure after this.
Late onset diseases eg Huntington’s disease (30-40 years) not selected in a way that early ones are eg sickle cell anaemia
Some genes selected early in life may be deleterious later (e.g. immune system, androgens)
Molecular/Cellular (non-programmed):
theory of ageing
Free radical damage to molecules
Increased frequency of senescence
System (non-programmed):
theory of ageing
Neuroendocrine alterations result in age related physiological changes.
Immunologic function declines- decreased resistance to infection, cancer & increased recognition of self.
Ageing genes: Syndromes
> Hutchinson-Guilford Progeria
> Werner syndrome
What is Hutchinson-Guilford Progeria?
Rare genetic disorder.
Mutation in LMNA encoding nuclear envelope protein: lamin A.
Affects RNA transcription & chromatin organisation.
Lack of DNA strand rejoining after irradiation.
Accelerated ageing (atherosclerosis). Usually die by 13.
What is Werner syndrome?
Mutation in WRN, DNA helicase family
‘caretaker of the genome’: DNA repair and transcription.
Baldness, hair and skin ageing, calicification of vessels, cancers, cataracts, arthritis, diabetes.
Die by age 50
Central control of ageing?
How many times do cells usually divide?
Approx. 50 times
Decline in proliferative capacity
Senescence
Cancer cells have no limit (immortal)
What happens to telomeres with age?
Telomeres= DNA sequences
Protect the ends of chromosomes
Progressive shortening with age
What are telomerases?
Reverse transcriptase.
Stabilizes telomere length.
Telomerase activity in 90% tumours
Lifestyle effect on ageing?
- sedentary= genetically old
- Telomeres shorter more quickly in inactive people
What is Molecular ageing?
Conformational change, aggregation, precipitation, amyloid formation
Ageing: catabolic chance driven?
Free radical effect on ageing?
Accumulation of oxidative damage in proteins & DNA
Damage to mitochondrial DNA.
Antioxidants to counter ageing (Vit C, E, β-carotene, 2-deoxy glucose)
Skin ageing features-
Wrinkles, pigmented lesions etc.
Sun exposure, air pollution, alcohol, poor nutrition.
Smoking- increase in metalloproteinase enzymes which break down collagen.
Calorific restriction to decrease ageing rate-
Reduced oxidant production by mitochondria- less ROS damage.
Induction of SIRT1- key regulator of cell defence.
Increased protein turnover- lack of accumulation of damaged protein.
Healthy life expectancy definition?
Summary measure of population health, estimates based on question ‘How is your health in general?’
Disability-free life expectancy definition?
Estimates based on those who answer yes to both:
Do you have any physical or mental health conditions or illnesses lasting or expected to last 12 months or more?
Does your condition or illness/do any of your conditions or illnesses reduce your ability to carry out day-to-day activities?
What is ‘Old age’?
What it means to age and be a particular age in a given society varies
This means that what ‘old age’ is varies and so it is socially constructed
What is ageing?
combination of biological, psychological and social processes that affect people as they grow older
- Physical changes to the body
- Shifts in mental processing capacity
- Changes in society and the social context in which people are ageing
Laslett (1989) proposed different dimensions to age and ageing (5)
Chronological (length of life measured in years since birth)
Biological (physical ageing, based on changes in health, fitness, functioning and appearance)
Social (norms and expectations relating to age)
Personal (moment in the life course reached in relation to personal aims)
Subjective (how we feel ‘inside’)