Health and community ageing Flashcards
(36 cards)
What is mortality shock
A reduction in life expectancy with a quick recovery
What causes a mortality shock
- Natural disasters e.g. Haiti earthquake
- Emergence of disease e.g. Nepalese peacekeepers brought cholera to Haiti
- Conflicts e.g. IS where prolonged conflict stops recovery
3 ageing diseases
- Hutchinson-Gilford syndorme
- Werner syndrome
- Down’s syndrome
What is Hutchinson gilford syndrome
- A genetic disorder where ageing manifests at a very early stage.
- Average age of death is 13
- Fragile body, large head, loss of hair, dwarfism
Causes of Hutchinson gilford syndrome
- A mutated lamin A protein, called prgerin. Has the last 50 amino acids missing.
- Causes a change in nuclear shape.
- Lamin A promotes genetic stability by maintain proteins in DNA repair
- There is an inability to repair DNA damage causing premature ageing.
Why is HGPS not a good model for ageing
- No increase risk of cancer
- High blood pressure is rare
- Dont suffer from mental degeneration or get Alzheimers
What is Werner syndrome
- Normal growth until puberty, then accelerated ageing
- Autosomal recessive
- Live to 40s - 50s
- Common cause of death is cancer and atherosclerosis (Build up of plaque in arteries)
Causes of werner syndrome
Limited cellular division capacity:
- Fibroblasts have fewer divisions
- Result in a loss of function in WRN, a DNA helicase
Faulty DNA replication at telomeres:
-WRN has a role in efficient replication of telomeres
Why is werner not a good model for ageing
- No high blood pressure
- No stroke
- No mental degeneration and Alzheimers
What is Down’s syndrome symptoms
- Greying/ loss of hair
- Early onset of vascular disease
- Early onset of Alzheimer’s disease
- Build of plaques and tangles (hallmarks)
3 types of downs syndrome
- Trisomy 21: An extra chromosome 21
- Translocation downs: Extra chromosome 21 attached to another chromosome
- Mosaic Down’s: Some cells are trisomic, others are not
Causes of Down’s syndrome
- Fibroblasts proliferate slowly
- There is downregulation of USP 16 which a critical regulator of DNA damage by removing ubiquitin from histones. Ubiquinated histones recruit DNA repair enzymes at sites of double breaks
Mutated age-1 gene
It encodes catalytic subunit of PI3K.
Leads to dysregulation of glucose metabolism
Linked to diet and caloric restriction
daf-2 gene
Allows C.elegans to enter a dauer state which double life span
APOE-4 allele
A risk factor for Alzheimer’s.
APOE removes plaque (amyloid beta)
APOE 4 Binds poorly to plaque (amyloid beta) and so there is a build up.
How to interfere with IIS pathway to decrease ageing
- Phagocytosis
- Caloric restriction (limiting damage due to oxidative phosphorlyation)
2 removal mechanisms
- Proteasome mediated
- Autophagy
How are proteins damaged
- Misfolded
- Reactive oxygen species (formed by leaked elctrons reacting with oxygen)
How do proteasomes degrade damage proteins
Made of a regulatory particle and a core particle. Where proteins are unfolded by the regulatory particle and degraded by the core particle.
Role of Autophagy
- Removes aggregates and damage organelles
- Also provides nucleotides, lipids and sugars under low nutrient conditions
Stages of macroautophagy
- Isolation membrane captures cytoplasmic contents forming an autophagosome
- Fuses with a lysosome becoming an autolysosme
- Hydrolytic enzymes degrade cytoplasmic cargo
What is microautophagy
Direct targeting of the lysosme
What is chaperone mediated autophagy
Via membrane channel
How is macroautophagy selective
Recruits a LC3-II protein that acts as a receptor for ubiquinated substrates
