Preventative Approaches to Ageing II

Question 1

How has the main cause of death changed in LMICs?

Answer 1

Used to be communicable and nutritional diseases

Now non-communicable diseases

Question 2

What are the current main strategies against diseases of ageing?

Answer 2

Society changes
Healthcare changes
Prevention strategies

Question 3

What is the aim of developing treatments for diseases of ageing?

Answer 3

Extend human healthspan - not lifespan

Question 4

What could be the effect of treating ageing itself?

Answer 4

May affect some/all diseases of ageing

Could provide treatment for previously untreatable disease

Question 5

What are the 2 main preventative treatment possibilities for diseases of ageing?

Answer 5

Nutrition

Pharmacological

Question 6

What is the effect of dietary restriction?

Answer 6

Extends lifespan

Improves health

Question 7

How does dietary restriction probably work?

Answer 7

Excess in normal diet - unclear what

Could be due to macronutrient ratios

Question 8

Which macronutrients could mediate the effect of dietary restriction?

Answer 8

Calories - probably not/not only
Fat
Sugar
Protein

Question 9

What are the effects of intermittent fasting in animals?

Answer 9

Increased lifespan

Increased healthspan

Question 10

What are the effects of intermittent fasting in humans?

Answer 10

Increased liver insulin sensitivity
Decreased BP
Increased neurogenesis
Decreased inflammation

Question 11

What is the issue with intermittent fasting in humans?

Answer 11

Willpower

Question 12

What is the aim of using drugs to prevent age-related diseases?

Answer 12

Give dietary restriction benefits with normal diet

Question 13

What is the mechanism of rapamycin action?

Answer 13

Inhibits TORC1

Question 14

What are the effects of rapamycin in mice?

Answer 14

Extends lifespan
Improves organ functioning - e.g. liver, heart
Improves response to influenza vaccine in older mice

Question 15

What is rapamycin currently used as in humans?

Answer 15

Immunosuppressant - fairly safe

Question 16

What are the benefits of other mTOR inhibitors over rapamycin?

Answer 16

Increase human vaccine efficiency more than rapamycin
Fewer side effects
Give long term decrease in respiratory infections after acute dose - acute treatment could have long-term effect

Question 17

How are animal drug trials to prevent age-related diseases often sexually dimorphic?

Answer 17

Usually better drug effect in females

Question 18

What is the mechanism of metformin action?

Answer 18

Activates AMPK

Question 19

What is metformin currently used to treat in humans?

Answer 19

T2D

Question 20

What is the effect of metformin on T2D patient outcomes?

Answer 20

Improves CVD outcomes

Some evidence for decreased cancer, increased cognitive function, increased lifespan

Question 21

What is the effect of senolytics in animals?

Answer 21

Improves health and age-related changes

Question 22

How would senolytic treatments be given?

Answer 22

Short repeated treatments

Question 23

Which disease is currently the focus of developing a senolytic treatment and why?

Answer 23

Osteoarthritis
No current treatment
Localised disease - do not need to give drug systemically - may decrease side effects

Question 24

Which metabolic treatment may be suitable for age-related disease prevention?

Answer 24

Nicotinamide replenishment