Clinical Ageing and Health Flashcards
Define a disease
-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
What is the study of disease called?
Pathology
Name some causes of disease
Pathogens, toxins, genetic mutations and cancer
Define ageing
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
How many stages do stress responses generally have and what are they?
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
What is cellular senescence?
A special (stress-induced) form of durable cell-cycle arrest that serves to prevent cancer in mammals
What does cellular senescence lead to?
- Telomere shortening and chromatin modification
- Persistent DNA damage response
- Senescence-associated secretory phenotype (SASP) - increased inflammatory cytokines/chemokines/proteases
What does cellular senescence entail?
-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
Does the number of senescent cells increase or decrease with age?
Increases, and rate of senescent cell accumulation accelerates
What can increase rate of senescent cell accumulation?
Exposure to toxins and/or cellular stress (e.g. smoking tobacco, which increases oxidant stress and exposes cells to thousands of toxic chemicals
What does senescence suppress?
Apoptotic cell clearance
What is autophagy?
Autophagy (‘self-eating’) is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation
What processes does autophagy play a critical role in?
-Homeostasis
-Development
-Stress adaptation
-Cellular differentiation
-Also required for recycling of cellular organelles e.g. mitochondria (‘mitophagy’)
What is defective regulation of autophagy involved in? (malfunction or abnormal control of the process of autophagy)
-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
What is inflammation essential for?
Protection from infection and clearance of apoptotic/damaged/aged cells (homeostasis)
Which chronic ageing diseases is dysregulation of inflammation involved in?
Cancer, CVD, autoimmune diseases, neurodegenerative diseases, clearance of senescent cells/aging and allergy
What does oxidative stress do?
-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
What is fibrosis?
-An increase in the deposition of matrix components
-Increase of matrix stiffness
-Altered cellular function
-Common examples are liver cirrhosis, kidney fibrosis and hypertension
What is oedema?
An increase in extracellular fluid in the spaces between the cells of the body
What are the two types of oedema and what do they entail?
- Localised - fluid retention in a particular part of the body. It is usually due to injury or an allergic reaction.
- 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
What are the different forms of oedema?
-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
What is hypertrophy and what can it impair?
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
What does diet have an influence on within cells?
-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
What is exercise important for?
Maintaining a healthy weight, as well as regulating many aspects of metabolism and protection from heart disease and cancer
