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CNM NUTRITION 2 S2 > 19. AGEING, MS & PARKINSON'S > Flashcards

19. AGEING, MS & PARKINSON'S Flashcards

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1
Q

What is hormesis?

A

A process in which exposure to a low level of stress or toxicity induces an adaptive beneficial effect in a cell or organism.

Examples include calorie restriction, phytochemicals, and exercise.

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2
Q

What does ‘allostatic load’ refer to?

A

The interaction of social, psychological, lifestyle, and nutritional factors with our genome that creates either healthy resilience to ageing or accelerated deterioration with age.

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3
Q

What is the mitochondrial theory related to ageing?

A

Mitochondria are the main source of reactive oxygen species (ROS), and mitochondrial dysfunction leads to apoptosis and is linked to MS, Alzheimer’s, and Parkinson’s diseases.

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4
Q

Define ‘inflammageing’.

A

Chronic low-grade inflammation that increases as we age, leading to age-related diseases.

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5
Q

What is the maximum lifespan potential (MLSP) of humans?

A

Over 100 years, which is four times higher than expected for a mammal of our size.

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6
Q

List three factors that promote chronic inflammation.

A
  • Pathogens
  • Damaged tissues
  • Altered gut microbiota
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7
Q

What role does Nrf2 play in cellular stress response?

A

Nrf2 is a transcription factor that upregulates genes related to the production of endogenous antioxidants.

Mechanism of Nrf2 Activation and Action:
Nrf2 Under Normal Conditions:

In healthy cells, Nrf2 is usually bound to an inhibitor protein called Keap1 in the cytoplasm. This binding keeps Nrf2 in an inactive form, preventing it from entering the nucleus.

Activation of Nrf2:

When the body experiences oxidative stress (excessive reactive oxygen species or ROS) or other stressors (e.g., toxins, inflammation), the Keap1-Nrf2 complex is disrupted.

This disruption allows Nrf2 to escape the cytoplasm and translocate to the nucleus.

Nrf2 in the Nucleus:

Once inside the nucleus, Nrf2 binds to antioxidant response elements (AREs) in the DNA, initiating the transcription of genes responsible for producing antioxidant enzymes and other detoxifying proteins.

These genes include:

Superoxide dismutase (SOD): Converts superoxide radicals into less harmful molecules.

Glutathione peroxidase (GPx): Reduces hydrogen peroxide to water, preventing oxidative damage.

NAD(P)H: Quinone oxidoreductase 1 (NQO1): Protects cells from oxidative damage by detoxifying reactive species.

Glutathione-S-transferase (GST): Helps in detoxification by binding to and neutralizing harmful substances.

Endogenous Antioxidant Production:

By activating the expression of these antioxidant genes, Nrf2 enhances the body’s natural defenses against oxidative damage, inflammation, and the harmful effects of toxins.

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8
Q

Fill in the blank: The process of ‘self-eating’ or digestion of worn-out cell components is known as _______.

A

autophagy

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9
Q

What are the hallmarks of ageing that autophagy defends against?

A
  • Genome instability
  • Telomere shortening
  • Epigenetic alterations
  • Loss of protein regulation
  • Insulin resistance
  • Cell senescence
  • Stem cell loss
  • Altered intercellular communication
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10
Q

How does social connection impact health in the elderly?

A

Social connection is a powerful anti-inflammatory and can reduce BMI, blood pressure, and inflammation.

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11
Q

What are advanced glycation end products (AGEs)?

A

Proteins modified by glycation that can bind to AGE receptors and promote inflammation.

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12
Q

List four nutrients beneficial for anti-ageing.

A
  • B vitamins
  • Omega-3 fatty acids
  • Magnesium
  • Vitamin D
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13
Q

What is the most common form of dementia?

A

Alzheimer’s disease.

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14
Q

Name three risk factors for dementia.

A
  • Chronic stress
  • Poor diet
  • Social isolation
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15
Q

What are amyloid plaques and tau proteins associated with?

A

Alzheimer’s disease pathology.

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16
Q

True or False: Mitochondrial dysfunction is a factor in Alzheimer’s disease.

A

True

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17
Q

What dietary habit is associated with long-lived Okinawan people?

A

Eating until 80% full, a philosophy termed ‘hara hachi bu’.

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18
Q

What is the function of phase I detoxification enzymes?

A

Transform xenobiotics, steroid hormones, and drugs into reactive intermediates.

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19
Q

Which plant compounds are thought to desensitize the aryl hydrocarbon receptor (AhR)?

A
  • Green tea
  • Turmeric
  • Quercetin
  • Resveratrol
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20
Q

What health conditions are AGEs associated with?

A
  • Accelerated ageing
  • Neurodegeneration
  • Diabetes
  • Cancer
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21
Q

What is the role of sirtuins in the body?

A

Improve insulin sensitivity, mitochondrial activity, cardiovascular health, and lower inflammation.

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22
Q

What are the four main types of dementia?

A
  • Frontotemporal dementia
  • Vascular dementia
  • Lewy body dementia
  • Alzheimer’s disease
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23
Q

What is the impact of exercise on ageing?

A

Exercise mitigates all the hallmarks of ageing and improves various health functions.

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24
Q

Fill in the blank: The process of mitochondrial quality control is referred to as _______.

A

mitochondrial dynamics

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25
What are the two proteins correlated with Alzheimer's disease pathology?
Amyloid beta and tau.
26
What characteristic features are associated with Alzheimer's disease pathology?
Amyloid plaques and misfolded tau proteins.
27
What drives amyloid production in the brain?
Infection, inflammation, and oxidative stress.
28
What is the role of amyloid beta in relation to Alzheimer's disease?
It is thought to be the brain's protective response to a threat rather than the cause.
29
What imaging techniques are used for diagnosing Alzheimer's disease?
Combined CT scan and MRI, combined PET scan and CT scan.
30
Who is Dr. Dale Bredesen?
A world leader in Alzheimer's research.
31
What are microglia?
Resident immune cells of the brain.
32
What are the three categories of Alzheimer's disease as defined by Dr. Bredesen?
* Inflammation or 'hot' * Atrophic or 'cold' * Cortical or 'toxic'
33
What is the difference between M1 and M2 microglia?
M1 microglia are pro-inflammatory while M2 microglia are anti-inflammatory.
34
What transcription factor supports the shift from M1 to M2 microglia?
Nrf2.
35
What is the impact of gut dysbiosis on Alzheimer's disease?
It leads to pro-inflammatory communication to TLRs on brain microglia.
36
What role does oxytocin play in relation to microglia-related inflammation?
It suppresses microglia-related inflammation.
37
What is the hippocampus's role in neurogenesis?
It is involved in memory storage, mood, and cognitive functions.
38
What is BDNF and its significance in Alzheimer's disease?
BDNF (brain-derived neurotrophic factor) is essential for the survival of cholinergic neurons and is significantly decreased in Alzheimer's disease.
39
What lifestyle factors can support BDNF levels?
* Exercise, yoga, dance * Environmental enrichment * Social enrichment * Polyphenols * Mediterranean diet
40
What is the main neurotransmitter that supports memory recall?
Acetylcholine.
41
What is Donepezil used for?
To raise levels of acetylcholine by inhibiting acetylcholinesterase.
42
What is a potential side effect of Donepezil?
Nausea and incontinence.
43
What is the relationship between aluminium and Alzheimer's disease?
Aluminium is a neurotoxin implicated in Alzheimer's disease.
44
What is meant by 'Type 3 diabetes' in relation to Alzheimer's disease?
It refers to the strong association between insulin resistance and Alzheimer's disease.
45
What dietary components are recommended by Dr. David Perlmutter for brain health?
* Whole unprocessed foods * Low GI foods * Healthy fats * Fatty fish * Plenty of water
46
What is the MIND diet?
A hybrid of the Mediterranean and DASH diets designed to protect against Alzheimer's disease.
47
What does the Ketoflex 12/3 diet entail?
Leaving 12 hours between the last meal of the day and the first meal the next day, and 3 hours between the last meal and bedtime.
48
What is the goal of the MEND protocol?
To optimize diet, reduce inflammation, improve insulin sensitivity, and support brain health.
49
What are some recommended supplements for Alzheimer's support?
* Vitamin C * Alpha lipoic acid * CoQ10 * Citicoline * Curcumin
50
True or False: Coconut oil can boost ketone levels and improve cognitive performance in Alzheimer's patients.
True.
51
What is the role of salivarius in gut health?
Reduces gut permeability and dysbiosis ## Footnote Salivarius is a probiotic that can help maintain gut health.
52
What is the recommended dosage of CoQ10 for mitochondrial support?
600 mg ## Footnote CoQ10 is essential for energy production in cells.
53
What is citicoline used for?
Synapse and mitochondrial support and CNS anti-inflammatory ## Footnote Citicoline is a brain health supplement.
54
Which nutrients are included in the anti-inflammatory combination?
* Curcumin (500 mg) * Vitamin D (2000 iu) * Omega-3 fatty acids (750 mg) ## Footnote These nutrients are known for their anti-inflammatory properties.
55
What does resveratrol protect against?
Misfolded amyloid and tau ## Footnote Resveratrol is a compound found in red wine with neuroprotective effects.
56
Name THREE diet and lifestyle interventions to support BDNF.
1. Exercise 2. Healthy diet 3. Stress management ## Footnote BDNF is critical for brain health and neuroplasticity.
57
What is the average age of diagnosis for relapsing-remitting MS?
30 ## Footnote This form of MS is the most common among patients.
58
What are some symptoms of MS?
* Visual impairment * Nerve tingling and numbness * Intestinal and urinary problems * Fatigue and weakness * Poor coordination and balance * Speech difficulties * Learning and memory issues * Difficulty walking * Emotional difficulties * Muscle spasm or tremors * Pain ## Footnote MS symptoms can vary widely among individuals.
59
What is clinically isolated syndrome (CIS) in MS?
If the symptoms of MS occur only once ## Footnote CIS can lead to a diagnosis of relapsing-remitting MS if a further relapse occurs.
60
Which T-cell subpopulations shift in MS?
Shift away from anti-inflammatory T-regulatory cells (T-regs) towards autoreactive Th17 T cells ## Footnote This shift contributes to the autoimmune nature of MS.
61
What are proposed risk factors for MS?
* Vitamin D deficiency * Raised BMI * Infections (e.g., Epstein-Barr virus) * Childhood trauma/stress * Homocysteine * Mitochondrial dysfunction * Cigarette smoke exposure * Certain autoimmune diseases * Environmental toxins ## Footnote Understanding these risk factors can help in prevention and management.
62
What is the impact of vitamin D on MS?
Helps shift adaptive immune system expression toward anti-inflammatory T-regs ## Footnote Sufficient vitamin D levels are linked to reduced MS relapse risk.
63
What is the key aim of MS therapy regarding vitamin K?
Promote the regeneration of oligodendrocytes and remyelination in the central nervous system ## Footnote Vitamin K is important for oligodendrocyte health.
64
What does obesity do in relation to MS?
Makes the blood-brain barrier more permeable leading to CNS inflammation ## Footnote Factor Explanation & Mechanism Chronic Inflammation **Fat tissue**—especially visceral fat—secretes pro-**inflammatory cytokines like IL-6, TNF-α,** and leptin, which can activate autoimmune responses and worsen MS inflammation. **Leptin Resistance** Leptin (a hormone from fat cells) normally regulates hunger and immunity. In obesity, leptin becomes chronically elevated, **promoting Th1/Th17 immune responses,** which are directly involved in MS pathogenesis. **Vitamin D Deficiency** Obese individuals tend to have lower bioavailable vitamin D, a critical immune-regulating nutrient that reduces MS risk and dampens autoimmune activity. **Gut Dysbiosis Obesity **alters gut microbiota, which can disrupt immune tolerance and trigger neuroinflammation—both key players in MS. Insulin Resistance Metabolic syndrome and insulin resistance increase systemic inflammation and oxidative stress, worsening demyelination and nerve damage. BBB Disruption **Obesity can weaken the blood-brain barrier (BBB)**, making it easier for immune cells to enter the brain and attack myelin..
65
What is the Swank diet?
A low saturated fat diet with under 15 g/day ## Footnote The Swank diet was developed to support MS patients.
66
What are the symptoms of Parkinson's disease?
* Characteristic tremor * Muscle rigidity * Shuffling gait * Constipation * Bradykinesia ## Footnote Symptoms often precede diagnosis by years.
67
What is the role of alpha synuclein in Parkinson's disease?
Forms protein aggregates called Lewy bodies that accumulate in dopamine neurons ## Footnote Misfolded alpha synuclein is a hallmark of Parkinson's pathology.
68
What is L-dopa used for in Parkinson’s disease?
It converts to dopamine in the CNS ## Footnote L-dopa is the most commonly prescribed medication for managing Parkinson's symptoms.
69
What is a DaT scan used for?
Helps to differentiate between Parkinson's disease and essential tremor ## Footnote Imaging techniques aid in diagnosing movement disorders.
70
How does obesity drive up brain inflammation in MS?
Leads to an upregulation of M1 microglia overwhelming the protective M2 ## Footnote M1 microglia are pro-inflammatory and can exacerbate MS symptoms.
71
What is the average deficiency level of vitamin K in MS patients compared to normal?
Around one-third of expected levels ## Footnote Vitamin K deficiency is common in MS patients.
72
What is the primary role of L-dopa in Parkinson's disease treatment?
L-dopa is the drug/protein derivative most commonly prescribed to PD patients. Primary to increase dopamine levels in the brain.
73
Why is L-dopa prescribed to Parkinson's disease patients?
Dopamine cannot cross the blood-brain barrier, but L-dopa can, converting into dopamine in the CNS.
74
What enzyme do serotonin-producing neurons use to convert L-dopa to dopamine?
Amino acid decarboxylase.
75
What negative effect can L-dopa have on serotonin neurons?
It can damage serotonin neurons, leading to negative psychological effects.
76
What is the function of a decarboxylase inhibitor in L-dopa treatment?
It inhibits L-dopa dopamine conversion outside the brain, increasing dopamine levels in the brain.
77
Which vitamin should be avoided when taking L-dopa medication?
Vitamin B6.
78
From which amino acid is L-dopa derived?
Tyrosine.
79
How can protein-containing meals affect L-dopa passage into the brain?
They may facilitate easier L-dopa passage into the brain.
80
What toxic intermediate is formed when dopamine is degraded by MAO-B?
DOPAL.
81
How much can L-dopa medication increase DOPAL levels?
By 18 times.
82
What protein does DOPAL interact with, leading to toxic Lewy bodies?
Alpha synuclein.
83
What is considered a protective strategy for dopaminergic neurons?
Slowing down MAO-B and speeding up DOPAL detoxification.
84
What percentage of dopaminergic neurons may be lost by the time of PD diagnosis?
70%.
85
What are two early warning signs of Parkinson's disease?
* Loss of sense of smell * Constipation.
86
What does the Braak hypothesis of PD theorize?
Misfolded alpha synuclein travels from an inflamed gut to the brain over a period of 10 years.
87
What type of foods does Dr. David Perlmutter advise for brain health?
* Whole unprocessed foods * Low GI foods * Healthy fats * Fatty fish.
88
What is the goal of the Metabolic enhancement for neurodegeneration (MEND) approach?
To optimise diet and reduce inflammation.
89
What lifestyle change is recommended to reduce inflammation and promote neurogenesis?
Exercise for 1 hour per day.
90
What should be tested if raised C-reactive protein is found?
Follow goals for omega-3 fatty acids and curcumin.
91
What are two recommended supplements for mitochondrial support?
* CoQ10 * Vitamin B complex.
92
What is a potential benefit of hyperbaric oxygen therapy for PD patients?
It can lessen psychiatric symptoms.
93
What should be avoided to prevent oxidative/nitrosative stress in the CNS?
EMFs from mobile phones and microwaves.
94
What is the role of Mucuna pruriens in Parkinson's disease treatment?
It contains L-dopa which crosses the blood-brain barrier.
95
Name three metals associated with an increased risk of PD.
Manganese, Iron, Mercury | also Aluminium, cadmium, cobalt, copper
96
What are two early warning signs that PD patients might have several years before diagnosis?
constipation and loss of smell
97
Which berries are MAO-B inhibitors and what toxic compound do they protect against?
Blueberries Anthocyanins, flavonoids Reduce MAO-B activity → preserve dopamine and serotonin 6-OHDA (6-hydroxydopamine) Mulberries Resveratrol, rutin Resveratrol inhibits MAO-B and activates SIRT1 for cell protection Protects against oxidative stress & mitochondrial toxins
98
Up to what length of time can constipation often precede a diagnosis of PD?
10 years
99
Name an agrochemical associated with PD.
Rotenone
100
What supplements might you choose to support mitochondria of a PD patient?
**Coenzyme Q10 (CoQ10) **- Part of the electron transport chain (ETC) → boosts ATP production - Antioxidant that neutralizes free radicals in mitochondria - May slow PD progression (high-dose studies) 300–1200 mg/day (divided doses with food) **Acetyl-L-Carnitine (ALCAR)** - Transports fatty acids into mitochondria for energy - Supports mitochondrial biogenesis - Neuroprotective against toxins like MPTP 500–2000 mg/day **Alpha-Lipoic Acid (ALA) **- Universal antioxidant (works in both fat- and water-soluble tissues) - Regenerates other antioxidants (like glutathione, Vit C, E) - Supports glucose metabolism in neurons 300–600 mg/day **Creatine -** Buffers cellular energy by replenishing ATP in high-demand tissues - May support muscle and neuronal function in PD 3–5 g/day **NAD⁺ precursors** (e.g., NMN, NR) - Support cellular metabolism and mitochondrial repair - Activate sirtuins (SIRT1) for neuroprotection NMN: 250–500 mg/day NR: 300–600 mg/day Magnesium (Threonate or Glycinate) - Co-factor for mitochondrial enzymes - Supports ATP production, neuronal firing, and sleep quality 200–400 mg/day **Vitamin B-complex **(especially B1, B2, B3, B6) - Crucial for mitochondrial energy metabolism and neurotransmitter synthesis - B1 (thiamine) has shown specific promise in PD symptom reduction B1: 300–600 mg/day (high-dose protocol under supervision) Others: As part of a high-potency B-complex **Glutathione (liposomal or IV) **- Master antioxidant that detoxifies ROS inside mitochondria - Low levels are common in PD; replenishing helps restore redox balance Liposomal: 500–1000 mg/day IV: 1200–2400 mg 2–3x/week (clinically administered)

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