The Ageing Process

Question 1

what is ageing?

Answer 1

progressive, generalised impairment of function resulting in a loss of adaptive response to disease

Question 2

what is involved in human ageing?

Answer 2

random molecular damage during cell replication
inactivity, poor diet, inflammation increase damage
reduction in body’s adaptive reserve capacity (resilience)

Question 3

what 7 factors contribute to ageing?

Answer 3

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

Question 4

what are telomeres?

Answer 4

end parts of chromosomes consisting of multiple repeats of a single motif which form a DNA loop

Question 5

what is the telomere motif in humans and how many times is it repeated (kilobases)?

Answer 5

TTAGGG

15 kilobases/repeats

Question 6

what happens to telomeres as we age?

Answer 6

progressively shortens with each cell division and eventually becomes too short to sustain cell replication leading to cell senescence

Question 7

what is the hayflick limit?

Answer 7

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

Question 8

what is telomerase?

Answer 8

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

Question 9

what changes in macromolecules can occur during ageing?

Answer 9

DNA mutation and breaks
lipid peroxidation
protein misfolding, aggregation and crosslinking

Question 10

what can cause macromolecular damage?

Answer 10

ionising radiation
reactive oxygen species (diet, radiation, inflammation)
extrinsic toxins (e.g bisphenols)

Question 11

what are the 4 main cellular responses to damage?

Answer 11

repair
apoptosis
senescence
malignant transformation

Question 12

name 3 repair mechanisms?

Answer 12

DNA repair
waste recycling (proteasomes, ubiquitin tagging)
stem cells

Question 13

summarise the disposable soma hypothesis

Answer 13

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

Question 14

describe antagonistic pleiotropy (an alternative theory of ageing)

Answer 14

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)

Question 15

huntingtons/cancer link

Answer 15

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

Question 16

what is frailty?

Answer 16

loss of homeostasis and resilience
increased vulnerability to decompression after a stressor event
increases risk of falls, delirium, disability and death

Question 17

how do frail people respond to illness compared to independent, fit people?

Answer 17

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

Question 18

what are the 2 main models of identifying frailty?

Answer 18

deficit accumulation (rockwood)
phenotypic (fried score)

Question 19

what is the deficit accumulation model?

Answer 19

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

Question 20

what is the phenotypic model?

Answer 20

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

Question 21

what is the electronic frailty index?

Answer 21

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)

Question 22

are frailty and multimorbidity the same?

Answer 22

no

often come hand in hand but can be multimorbid but not frail and can be frail but without multiple morbidities

Question 23

are lifestyle factors relevant in over 75s?

Answer 23

yes

not smoking, physical activity and being social can increase survival in people 75+

Question 24

how can calorie restriction affect lifespan?

Answer 24

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