Ageing

Question 1

‘
Allostatic load’ or ‘overload theory’

Answer 1

• Social, psychological, lifestyle and nutritional factors all interact with our genome to create either healthy resilience to ageing or accelerated deterioration with age.
• Exposure to toxins (environment, household, cosmetics), inadequate exercise, poor nutrition, high stress, genetic susceptibility, chronic inflammation and dysbiosis all play a role at a physiological and molecular level.

Question 2

Mitonchodial theory

Answer 2

• Mitochondria are considered to be the main source of ROS in a cell.
• Oxidative stress within mitochondria leads to mtDNA mutations, reduced ATP and energy.
• Mitochondrial dysfunction leads to apoptosis (programmed cell death).
• Mitochondrial dysfunction is linked to MS, Alzheimer’s and Parkinson’s diseases and many chronic inflammatory diseases.

Question 3

Inflammageing

Answer 3

• Chronic low grade inflammation increases as we age (inflammageing) leading to many age related diseases.
• Pathogens, damaged tissues, altered gut microbiota, antibiotics, steroids, and antihistamines all promote chronic inflammation.
• Inflammageing is the result of pathological stimulation of the innate immune system.
• Alzheimer’s disease is associated with inflammageing of the brain.

Question 4

Maximum lifespan
potential

Answer 4

• Ageing is mostly considered in a negative way but, in general, humans are exceptionally good at dealing with the ageing process.
• Humans have a maximum lifespan potential (MLSP) of over 100 years. This is FOUR times higher than expected for a mammal of our size!
• Understanding and implementing human anti- ageing strategies will improve our healthspan ’ as well as lifespan.

Question 5

Hormesis

Answer 5

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

Examples:
* Calorie restriction
* Phytochemicals
* Exercise
* Cognitive stimulation
* Intermittent cold and heat

A healthy body responds to mild stress by increasing the production of endogenous antioxidants

Question 6

Nrf2

Answer 6

• Nrf2 is a transcription factor which senses cellular
  stress and then responds by upregulating genes
  relating to the production of endogenous antioxidants.
• Nrf2 increases the expression of glutathione enzymes , superoxide dismutase, catalase and phase II detoxification enzymes.

Question 7

Calorie restriction and exercise

Answer 7

• Calorie restriction and exercise induce stress partly by depleting cellular energy decrease ATP and NADH. increase ADP and NAD.
• Low cellular energy activates AMPK , a pro longevity protein.
• Low cellular energy also activates the sirtuins (SIRT 1-7 ), a family of anti ageing proteins.

Question 8

Autophagy and mitophagy

Answer 8

• AMPK and sirtuins initiate a process called autophagy (self eating), where worn out or damaged cellular components are digested to improve
  the quality of the whole organism.
• Autophagy of mitochondria is known as mitophagy. 9-25 days depending on organ.

Question 9

9 key signatures of ageing

Answer 9

• Genome instability.
• Telomere shortening.
• Epigenetic alterations.
• Loss of protein regulation and disposal (a hallmark of Alzheimer’s and Parkinson’s diseases)
• Insulin resistance and poor nutrient sensing.
• Cell senescence (biological ageing)
• Stem cell loss.
• Altered intercellular communication.

Question 10

Detoxification and ageing

Answer 10

• Too fast phase 1
• Hormesis supports phase II and III detoxification

Question 11

Calorie restriction, intermittent fasting and fasting

Answer 11

• Activate sirtuins , the anti ageing proteins.
• Sirtuins improve insulin sensitivity , mitochondrial activity , cardiovascular health , fat metabolism DNA integrity and also lower inflammation
• Promote autophagy to aid cellular rejuvenation.
• Increase adiponectin , an adipokine associated with longevity.
• Ketogenic diets may mimic some of the health benefits of fasting by shifting metabolism toward beta oxidation and ketone synthesis. Ketones protect an ageing brain.

Question 12

Advanced glycation end products or AGEs

Answer 12

• Proteins modified by glycation are able to bind to AGE receptors (RAGEs) and promote inflammation.
• AGEs are strongly associated with accelerated ageing, neurodegeneration, diabetes and cancer.