Ageing, Alzheimers, MS & Parkinsons Disease Flashcards
What is hormesis?
A process in which exposure to a low level of stress or toxicity induces an adaptive beneficial effect in a cell or organism.
A little stress increases the lifespan (or “health span”). True or false.
True. It’s called hormesis
List 5 contributors to ageing at physiological and molecular level
Exposure to toxins
Inadequate exercise
Poor nutrition
High stress
Genetic susceptibility
Chronic inflammation
Gut dysbiosis
_____________ dysfunction is a cause of ageing and is linked to MS, Alzheimer’s and Parkinsons diseases
Mitochondrial dysfunction
What is inflammageing?
Chronic low-grade inflammation increases as we age. Inflammageing is the result of pathological stimulation of the innate immune system.
Alzheimers Disease is associated with inlammageing of the _______
Brain
Give 2 examples of things that could contribute to hormesis
Calorie restriction
Phytochemicals
Exercise
Cognitive stimulation
Intermittent cold and heat
How does a healthy body respond to mild stress?
By increasing production of endogenous antioxidants
By increasing cellular quality control mechanisms
List 3 endogenous anti-oxidants increasingly produced by the body during hormesis / as a result of mild stress.
Glutathione
Catalase
Superoxide dismutase
Phase II detox enzymes
_______ is a transcription factor that senses cellular stress, and then responds by up regulating genes relating to the production of endogenous antioxidants (glutathione, SOD, etc)
Nrf2
Which 2 anti-ageing proteins are triggered by calorie restriction and exercise?
AMPK
Sirtuins (SIRT 1-7)
During a period of low cellular energy, AMPK and sirloins initiate a process called ___________ (self eating)
Autophagy
Which 2 anti-ageing proteins trigger autophagy during periods of low cellular energy?
Sirtuins
AMPK
What is autophagy of mitochondria called?
Mitophagy
In which 2 pathologies is mitophagy defective, resulting in low brain energy?
Alzheimers
Parkinsons
List 3 of the 9 key signatures of ageing
Telomere shortening
Genome instability
Epigenetic alterations
Loss of protein regulation and disposal
Insulin resistance
Cell senescence (biological ageing)
Stem cell loss
Altered callular communication
Excess phase 1 detoxification is linked to ageing and cancer. True or false?
True
Why is excess Phase 1 detoxification linked to ageing and cancer?
Because Phase 1 transforms xenobiotics, hormones and drugs into REACTIVE INTERMEDIATES, which are harmful if Phase II can’t keep up.
Phase 1 detox is important, but not too quickly!
List 3 plant compounds that can slow down phase 1 metabolism, protecting against cancer.
Turmeric
Green tea
Quercetin
Resveratrol
Garlic
Ginger
Which phases of liver detoxification does hormesis support?
Phase II and III
Exercise induces levels of PGC1-alpha protein. But what does it do?
Enables the synthesis of brand new mitochondria, through mitochondrial biogenesis
Obese and insulin resistant individuals present with mitochondrial dysfunction and reduced biogenesis. True or false?
True
What health conditions are AGES associated with?
Cancer
Diabetes
Neurodegeneration
Accelerated ageing
Name the most common form of dementia (60-80% of all cases).
Alzheimers Disease
List 5 risk factors for dementia
Chronic / acute stress
PPI medication
Poor diet
Vit & mineral deficiencies
Smoking
Alcohol
Poor lifestyle
Vaccinations
Hypertension
Diabetes
Mental Inactivity
Obesity
Physical inactivity
Social isolation
Environmental toxins
APoE polymorphism
Mid-life depression
What is APoE?
Apolipoprotein E (ApoE) is a major cholesterol carrier that supports lipid transport and injury repair in the brain.
Which two proteins are correlated with Alzheimers Disease pathology?
Amyloid beta and tau
Name two brain-centred pathologies in which you might find Lewy bodies
Levy body dementia
Parkinsons disease
What are the signs/symptoms of Alzheimers disease?
Progressive loss of memory, language and reasoning.
What is the main reason (NOT cause) of Alzheimers disease pathology?
Amyloid plaques and mis-folded tau proteins
What drives amyloid production in Alzheimers disease?
Infection
Inflammation
Oxidative stress
Diagnosis of Alzheimers disease is via brain scan (CT scan + MRI, or CT scan + PET scan). True or false?
True
What are the resident nerve cells of the brain called?
Microglia
Which transcription factor supports a shift from M1 (inflammatory) to M2 (anti-inflammatory, neuroprotective) microglia in the brain, positively supporting Alzheimers disease?
Nrf2
Which chemical/neurotransmitter, produced during enriched social interactions, can act through the vagus nerve to suppress microglia-related inflammation?
Oxytocin
In what way is oral dysbiosis significantly associated with increased Alzheimers risk?
Via P.gingivalis (from periodontitis)
Where in the brain does neurogenesis occur?
In the hippocampus
Which part of the brain is involved in memory storage, mood and cognitive functions?
The hippocampus
_______ is a neuroprotective protein essential for the survival of cholinergic neurone. Levels of this are significantly decreased in Alzheimers.
BDNF (Brain-derived-neurotrophic factor)
Healthy gut microbiota support BDNF production so are critical in Alzheimers support. True or false?
True
Name a neurotrophin
BDNF (Brain-derived-neurotrophic factor)
Which neurotransmitter do Alzheimers drugs attempt to raise?
Acetylcholine (anti-inflammatory neurotransmitter)
How can you support acetylcholine in Alzheimers without medication?
Acetylcholine is made of mitochondrial Aceytl-CoA and dietary choline. Support these! Healthy diet and lifestyle.
Which metal is implicated in Alzheimers disease
Aluminium
Aluminium concentrations are significantly raised in the brains of patients with Alzheimers Disease. True or false?
True
How does 20g/day coconut oil support Alzheimers?
By boosting ketones for brain energy
__________ ___________ is an auto-immune disease that can lead to neurodegeneration.
Multiple Sclerosis
What is the name of the cells that produce the myelin sheath?
Oligodendrocytes
What is the myelin sheath?
A fat and protein compound that wraps around nerves to support nerve impulses
What is the pathophysiology of multiple sclerosis?
Autoreactive and inflammatory immune cells infiltrate the blood brain barrier and attack the myelin sheath.
If sustained, this leads to loss of oligodendrocytes and neurodegeneration
What is the average of of diagnosis for relapsing-remitting MS?
30 years old
There are 2 types of MS, list them.
- Relapsing-remitting (85%)
- Primary progressive (15%)
Describe primary progressive MS
Continuous and progressive loss of neurological function with no remission.
Average age of diagnosis is 45.
List 4 signs/symptoms of multiple sclerosis
Visual impairment
Nerve tingling / numbness
Intestinal / urinary problems
Fatigue and weakness
Poor coordination and balance
Speech difficulties
Learning and memory issues
Difficulty walking
Emotional difficulties
Muscle spasm/tremors
Pain
What is ‘Clinically Isolated Syndrome’? (CIS)
When symptoms of MS occur only once.
Relapsing-remitting MS often progresses to secondary progressive MS after ___ - ___ years
10 - 30 years
List 3 proposed risk factors for MS
Vitamin D deficiency
Infections (e.g Epstein Barr)
Childhood trauma / stress
Homocysteine
Mitochondrial dysfunction
Cigarette smoke exposure
Certain autoimmune diseases
Environmental toxins
Key vitamin deficiencies - D, K, B12
Obesity
MS is considered to be a T-call mediated disease, with a shift in T-cell populations from anti-inflammatory T-rg cells, towards auto reactive Th__ cells.
Th17
List 2 of the major vitamin deficiencies found in MS patients
Vitamin D - deficiency causes more brain lesions and increased relapses.
Vitamin K - Gas6, a vitamin K-dependant anti-inflammatory protein protects oligodendrocytes and promotes remyelination.
Vitamin B12
Why is obesity a risk factor for MS?
- It makes the blood-brain barrier more permeable
- It raises leptin, which is associated with CNS inflammation
- Leptin increases levels of Th17 autoreactive cells
- Upregulates M1 microglia, overwhelming protective M2
Thymic involution (atrophy) amplifies the production of auto reactive T-cells and predisposes a person to MS. What life event can cause thyme involution?
Childhood trauma / abuse
The Swank diet is for which pathology?
Multiple Sclerosis
Which is the second most common neurodegenerative disorder after Alzheimers disease?
Parkinsons Disease
In which disease is there a gradual loss of dopamine-producing neurons in a part of the brain called the substantia nigra?
Parkinsons
What leads to the characteristic tremor and movement disorders seen in Parkinsons disease?
Loss of dopamine supply to the striatum area of the brain.
List 3 signs/symptoms of Parkinsons disease
Pill rolling tremor
Muscle rigidity
Shuffling gait
Constipation
Loss of sense of smell
Slow movement, facial expressions and speech
List 3 causes / risk factors of Parkinsons Disease
Age, heredity, sex
Mitochondrial dysfunction
Oxidative stress
Traumatic brain injury
Pesticides/herbicides
Heavy metal toxicity
Stress / depression
Recreational drugs
Essential tremor is a condition that can easily be mistaken for ____________ ___________
Parkinsons Disease
Which is the signature misfiled protein in Parkinsons disease?
Alpha Synuclein
What do Alzheimers Disease and Parkinsons have in common?
They both have an mis-folded protein associated with their pathology.
L-Dopa, the drug used in Parkinsons Disease, is derived from which amino acid?
L-tyrosine
