The Ageing Process

Question 1

Define ageing?

Answer 1

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

Question 2

Features of human ageing?

Answer 2

Random molecular damage during cell replication

Inactivity, poor diet, inflammation, i.e: disease states, increase damage

Reduction in body’s adaptive reserve capacity (resilience)

Question 3

Potential factors contribution to the ageing process?

Answer 3

Mutations in chromosomes and mitochondrial DNA

Intracellular aggregates, e.g: proteins
Extracellular aggregates, e.g: glycosylated cross-links (often accumulate more in diabetics)

Cellular loss (lack of stem cels / cell replacement with age)

Cell senscence (useless / harmful cells)

Question 4

What is a telomere?

Answer 4

End part of chromosome arm; it consists of multiple repeats (TTAGGG in humans), forming a DNA loop of variable length

As the cell replicates, it shortens and so each cell has a limit on the no. of times it can replicate; eventually, this leads to cell senescence (AKA Hayflick limit)

Question 5

Issues with the Hayflick limit?

Answer 5

Most human cells do not divide enough times for it to be a limiting factor

However, telomeres are able to provide a marker of biological age

Question 6

What is telomerase?

Answer 6

Ribonucleoprotein complex that can re-extend the shortened telomeres (adding on more repeats)

It is active in cells that need to divide many times, e.g: immune cells, stem cells; it is less active in other cell types, which suffer from progressive telomere shortening

Question 7

Mechanisms by which damage to macromolecules can occur?

Answer 7

DNA mutations, breaks

Lipid peroxidation (leading to the formation of excessive reactive oxygen species)

Protein misfolding, aggregation, cross-linking

Question 8

Potential causes of macromolecule damage?

Answer 8

Ionising radiation, reactive oxygen species (from diet, radiation, inflammation) and extrinsic toxin, e.g: bisphenols (BPA)

Question 9

4 main cellular responses to damage?

Answer 9

• Repair
• Apoptosis
• Senscence
• Malignant transformation

Question 10

Why does damage accumulate if there are repair and regeneration mechanisms?

Answer 10

Theories:

• Disposable soma hypothesis - repair of a body uses energy and, once the body has reproduced, there is little evolutionary value in repairing that body, as the genes have passed on ; new generation requires energy and resources
• Antagonistic pleiotropy - genes may have beneficial effects early in life but the same genes may have deleterious effects late; these are usually inherited, to benefit early life, but may act as a “time-bomb” in later life

Question 11

Define frailty?

Answer 11

Loss of homeostasis and frailty; after a stressor event, there is increased vulnerability to decompensation, leading to an increased risk of falls, delirium, disability and death

E.g: should a minor illness occur in a frail patient, they suffer a larger drop in function) from an initial low standard) and spend a longer time recovering than a young, fit patient
They may not return to normal homeostasis

Question 12

Cycle of frailty?

Answer 12

Genetic and environmental factors lead to cumulative molecular and cellular damage, resulting in reduced physiological reserve:
• Brain
• Endocrine
• Immune
• Skeletal muscle
• CV and respiratory
• Renal

Decreased physical activity and nutritional factors can contribute to the development of frailty

Following a stressor event, frail patients can experience falls, delirium, fluctuating disability and this further reduces their physiological reserve

Question 13

Methods of measuring frailty?

Answer 13

2 models:

Deficit accumulation - take a number of body systems (20-80) and count the no. that have a deficit; the index is the deficits divided by the total no. of systems, producing a no. between 0 and 1

Phenotypic, e.g: Fried score - 1 point is given for each of:
• Unintentional weight loss
• Low grip strength 
• Self-reported exhaustion
• Low physical activity levels
• Slow walking speed

0 = non-frail, 1-2 = pre-frail, 3/more = frail

Question 14

Describe occurrence of multi-morbidity

Answer 14

i.e: multiple chronic conditions; most people with a chronic issue are multi-morbid

Many older adults have ≥3 chronic conditions

NOTE: multi-morbidity and frailty are not the same thing; a patient can be:
• Frail with no multi-morbidity
• Robust and no multi-morbidity
• Multi-morbidity and robust
• Multi-morbidity and frail

Question 15

Best ways to ensure health in old age?

Answer 15

Deliver people into old age in a healthy state

Physical activity in old age

Calorie restriction (personal choice)

Question 16

Define a centenarian?

Answer 16

Person who is 100/more years old; typically non-smokers who are slim, with few conditions

They tend to keep friends and be practical and strong

Question 17

Main medical features/presentations of old age?

Answer 17

Falls

Immobility

Delirium