The Ageing Process Flashcards
what is ageing?
progressive, generalised impairment of function resulting in a loss of adaptive response to disease
what is involved in human ageing?
random molecular damage during cell replication
inactivity, poor diet, inflammation increase damage
reduction in body’s adaptive reserve capacity (resilience)
what 7 factors contribute to ageing?
mutations in chromosomes
mutations in mitochondria
intracellular aggregates
extracellular aggregates
cellular loss (lack of stem cells/cell replacement)
cell senescence (useless/harmful cells, cells stop dividing)
extracellular protein crosslinks
what are telomeres?
end parts of chromosomes consisting of multiple repeats of a single motif which form a DNA loop
what is the telomere motif in humans and how many times is it repeated (kilobases)?
TTAGGG
15 kilobases/repeats
what happens to telomeres as we age?
progressively shortens with each cell division and eventually becomes too short to sustain cell replication leading to cell senescence
what is the hayflick limit?
suggested limit to the number of times a cell can divide, however most human cells don’t divide enough times for this to be a limiting factor
what is telomerase?
ribonucleoprotein complex which can re-extend the shortened telomeres
active in cells which need to divide many times (immune cells, stem cells etc)
less active in other cells which therefore suffer from telomere shortening
what changes in macromolecules can occur during ageing?
DNA mutation and breaks
lipid peroxidation
protein misfolding, aggregation and crosslinking
what can cause macromolecular damage?
ionising radiation
reactive oxygen species (diet, radiation, inflammation)
extrinsic toxins (e.g bisphenols)
what are the 4 main cellular responses to damage?
repair
apoptosis
senescence
malignant transformation
name 3 repair mechanisms?
DNA repair
waste recycling (proteasomes, ubiquitin tagging)
stem cells
summarise the disposable soma hypothesis
hypothesis which states that once reproduction has occurred (had children), the body doesn’t put as much effort into repairing itself and using resources and energy as the genes have already been passed on and maintaining good health is of little evolutionary value
describe antagonistic pleiotropy (an alternative theory of ageing)
genes have beneficial effects early in life but then have deleterious effect later in life (e.g the huntingtons gene)
these genes tend to be inherited as they benefit early life (at age where people have kids)
huntingtons/cancer link
repeat of CAG codon causes formation of small interfering RNA (siRNA) which is toxic to nerve cells but also even more toxic to cancer cells
huntingtons patients therefore have a much lower rate of cancer
what is frailty?
loss of homeostasis and resilience
increased vulnerability to decompression after a stressor event
increases risk of falls, delirium, disability and death
how do frail people respond to illness compared to independent, fit people?
independent people: functional abilities drop sharply a little for a short time then return to baseline function
frail: functional abilities drop sharply but further and for a linger time and don’t return to full baseline function, so abilities are slightly less afterwards
what are the 2 main models of identifying frailty?
deficit accumulation (rockwood) phenotypic (fried score)
what is the deficit accumulation model?
take a large number of body systems (20-80)
count how many have a deficit
index is deficits divided by total number of systems
number between 0 and 1, closer to 1 = more frail
what is the phenotypic model?
1 point each for unintentional weight loss low grip strength self-reported exhaustion low physical activity levels slow walking speed 0 = non-frail 1-2 = pre-frail 3+ = frail
what is the electronic frailty index?
method of showing frailty
36 features extracted from GP records (disease, abnormality, injury, mobility, social isolation etc)
added together and transformed to a proportion between 0 and 1 (closer to 1 = more frail)
are frailty and multimorbidity the same?
no
often come hand in hand but can be multimorbid but not frail and can be frail but without multiple morbidities
are lifestyle factors relevant in over 75s?
yes
not smoking, physical activity and being social can increase survival in people 75+
how can calorie restriction affect lifespan?
reducing calorie intake by 50% and having well balanced diet and increase lifespan
can postpone malignancy and age related changes in immune system
can limit free radical damage
