Aging process

Question 1

Define ageing

Answer 1

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

Question 2

what are the 3 key points for the human ageing process ?

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 is a telomere and what does it consist of ?

Answer 3

• A telomere is the end part of each chromosome arm
• It consists of multiple repeats of a single motif (TTAGGG in humans) which form a DNA loop

Question 4

What happens to a telemere with each cell replication and what does this progressive process result in ?

Answer 4

It progressively shortens with each cell replication, and eventually becomes too short to sustain cell replication – this then leads to cell senescence

Question 5

What is the hayflick limit ?

Answer 5

The number of times a normal human cell population will divide until cell division stops (most human cells dont divide enough for this to be a limiting factor)

Question 6

What is telomerase ?

Answer 6

• An ribonucleoprotein complex – telomerase – that can re-extend the shortened telomeres. The complex is active in some cells (e.g. immune cells, stem cells) which need to divide many times.
• It is less active in many other cell types, which therefore suffer from progressive shortening of telomeres over time

Question 7

What is some of the damages which can occur to macromolecules (very large protein molecules)?

Answer 7

• DNA mutation, breaks
• Lipid peroxidation
• Protein misfolding, aggregation, crosslinking

Question 8

What are some of the causes of damage to protein molecules in the body?

Answer 8

• Ionising radiation
• Reactive oxygen species (diet, radiation, inflammation)
• Extrinsic toxins (e.g. bisphenols)

Question 9

What are the 4 different responses which DNA damage can cause ?

Answer 9

1. Repair
2. Apoptosis (cell death)
3. Senescence (the condition or process of deterioration with age)
4. Malignant transformation

Question 10

We know that repair mechanisms exist in the body:

• DNA repair
• Waste recycling (e.g. proteasomes, ubiquitin tagging)
• Stem cells

What is the hypothesis of why we dont just repair all damage to cells ==> resulting in accumulation of damage i.e. ageing and malignancy?

Answer 10

1. Maintaining a body by repairing all damage takes a huge amount of energy and resource – and is thus not usually feasible
2. Once the body has reproduced, there is little evolutionary value in repairing and maintaining that body, as the genes have been passed on
3. So once reproductive age is over, damage is not repaired at the same rate as it accumulates. This eventually leads to multiple systems failures and the death of the organism

Question 11

What are the key points meant by fraility of older people

Answer 11

• Loss of homeostasis and resilience
• Increased vulnerability to decompensation after a stressor event
• Increases risk of falls, delirium, disability, death

Question 12

Appreicate this pic on the vulnerability of older people to a sudden change in health status after minor illness

Answer 12

Green line – fit older person who after a minor infection has small deterioration then returns to homeostasis

Red line – frail older person who after similar infection undergoes larger deterioration, which may be functional impairment, and never returns to homeostasis

Question 13

What are the 2 main models for assessing frailty ?

Answer 13

Deficit accumulation (Rockwood):

1. Take a large number of body systems (typically 20-80) Count how many of them have a deficit (e.g. low walking speed, renal impairment, diabetes, cognitive impairment, impaired balance)
2. Then divide the no. of deficits/the total no. of systems
3. Number between 0 and 1

Phenotypic (e.g. Fried score):

1 point each for:

1. Unintentional weight loss
2. Low grip strength
3. Self-reported exhaustion
4. Low physical activity levels
5. Slow walking speed

• 0 = non-frail
• 1-2 = pre-frail
• 3 or more = frail

Question 14

What is meant by multimorbidity and what is the prevelance of it in old age ?

Answer 14

• Most people with a chronic condition are multimorbid
• >50% older adults ≥3 chronic conditions i.e. it is having multiple chronic conditions
• Multimorbidity results in Higher rates adverse events, poorer quality life, greater healthcare use, institutionalisation, disability, death

Question 15

Is multimorbidity and frailty the same thing ?

Answer 15

No - someone have have multiple morbidities but not be frail and someone can be frail but not have multiple morbidites (but i do imagine they often come paired together)

Question 16

What are the medical characterisitics of old age ?

Answer 16

• Multimorbidity
• Multiple medications
• Illnesses can present in atypical ways
• Falls, immobility, delirium
• Need for rehabilitation