Clinical Ageing and Health

Question 1

Define a disease

Answer 1

-A particular abnormal condition that affects part or all of an organism not caused by
external force or injury.
-Broadly refers to any condition
that impairs the normal functioning of the body

Question 2

What is the study of disease called?

Answer 2

Pathology

Question 3

Name some causes of disease

Answer 3

Pathogens, toxins, genetic mutations and cancer

Question 4

Define ageing

Answer 4

A multifactorial process in which a gradual loss of homeostasis results in impaired immunity, perturbed metabolism and declining regenerative capacity.

It has been described as a duel between damage accumulation from intrinsic and extrinsic stressors and cellular responses to counteract damage

Question 5

How many stages do stress responses generally have and what are they?

Answer 5

3 stages - an alarm phase, a resistance/recovery stage, loss of homeostasis if stress is sustained leading to cellular exhaustion, typified by loss of replicative capacity, senescence and perturbed proteostasis, all markers of biological ageing

Question 6

What is cellular senescence?

Answer 6

A special (stress-induced) form of durable cell-cycle arrest that serves to prevent cancer in mammals

Question 7

What does cellular senescence lead to?

Answer 7

1. Telomere shortening and chromatin modification
2. Persistent DNA damage response
3. Senescence-associated secretory phenotype (SASP) - increased inflammatory cytokines/chemokines/proteases

Question 8

What does cellular senescence entail?

Answer 8

-Durable cell cycle arrest (not always irreversible)
-Expression of anti-proliferative genes e.g. p16, p21
-Activation of damage sensing pathways, e.g. p38MAPK and NFkB

Question 9

Does the number of senescent cells increase or decrease with age?

Answer 9

Increases, and rate of senescent cell accumulation accelerates

Question 10

What can increase rate of senescent cell accumulation?

Answer 10

Exposure to toxins and/or cellular stress (e.g. smoking tobacco, which increases oxidant stress and exposes cells to thousands of toxic chemicals

Question 11

What does senescence suppress?

Answer 11

Apoptotic cell clearance

Question 12

What is autophagy?

Answer 12

Autophagy (‘self-eating’) is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation

Question 13

What processes does autophagy play a critical role in?

Answer 13

-Homeostasis
-Development
-Stress adaptation
-Cellular differentiation
-Also required for recycling of cellular organelles e.g. mitochondria (‘mitophagy’)

Question 14

What is defective regulation of autophagy involved in? (malfunction or abnormal control of the process of autophagy)

Answer 14

-Parkinson’s disease - increase in mitochondrial damage and defective mitophagy leads to Parkinson’s
-Lysosomal storage disorders - progressive accumulation of undigested macromolecules within the cell, a family of disorders caused by inherited gene mutations that perturb lysosomal homeostasis
-Crohn’s disease - inflammatory bowel disease
-Cancer - impaired during initiation but increases with malignancy
-Atherosclerosis - impaired autophagy promotes disease and likely to drive heart attack process of plaque erosion

Question 15

What is inflammation essential for?

Answer 15

Protection from infection and clearance of apoptotic/damaged/aged cells (homeostasis)

Question 16

Which chronic ageing diseases is dysregulation of inflammation involved in?

Answer 16

Cancer, CVD, autoimmune diseases, neurodegenerative diseases, clearance of senescent cells/aging and allergy

Question 17

What does oxidative stress do?

Answer 17

-Damages proteins and DNA, inhibiting normal cellular function
-This triggers DNA damage response
-Activates the anti-oxidant protection system controlled by the transcription factor Nrf2.

However, there is a cost to the cell for strongly activating the Nrf2 system chronically

Question 18

What is fibrosis?

Answer 18

-An increase in the deposition of matrix components
-Increase of matrix stiffness
-Altered cellular function
-Common examples are liver cirrhosis, kidney fibrosis and hypertension

Question 19

What is oedema?

Answer 19

An increase in extracellular fluid in the spaces between the cells of the body

Question 20

What are the two types of oedema and what do they entail?

Answer 20

1. Localised - fluid retention in a particular part of the body. It is usually due to injury or an allergic reaction.
2. Generalised - affects the whole body. It usually causes puffy ankles after standing and puffy eyes after lying down for a while. This may be due to an underlying heart condition

Question 21

What are the different forms of oedema?

Answer 21

-Cerebral oedema - fluid on the brain, usually due to infection (meningitis) or serious brain disease (stroke or brain tumour)
-Pulmonary oedema - fluid on the lungs, usually due to heart disease
-Lymphoedema - a build-up of lymph fluid when lymph channels are damaged - e.g., after breast cancer surgery
-Idiopathic - no known cause
-Can prevent mobility or proper function of that tissue

Question 22

What is hypertrophy and what can it impair?

Answer 22

Hypertrophy is the increase in size of either cells or tissues
This can impair the normal function especially in the heart, where it reduces contractile efficiency

Question 23

What does diet have an influence on within cells?

Answer 23

-The susceptibility to disease as it affects the ability of the body to maintain an efficient immune system
-Recovery and repair
-Maintenance of normal cellular function
-Protection from oxidative stress

Question 24

What is exercise important for?

Answer 24

Maintaining a healthy weight, as well as regulating many aspects of metabolism and protection from heart disease and cancer