Lecture 8

Question 1

What can caloric restriction cause?

Answer 1

Increased lifespan

Shown in multiple vert and invert species

Question 2

How does restriction affect lifespan?

Answer 2

There is evidence that longevity brought about by dietary restriction is linked to nutrient sensing pathways, TOR and AMPk

Question 3

What is nutrient sensing at a cellular level?

Answer 3

2 main protein kinase pathways that sense nutrients- AMPK and TOR

Question 4

What is AMPk?

Answer 4

Responds to decline in glucose, AAs, fatty acids and increasing AMP:ATP ratio (low energy)

Triggers catabolic processes, release of stored nutrients, inhibition of growth and reproduction

Question 5

What is TOR

Answer 5

Stimulated by high ATP and nutrients, particularly BCAAs and the glucose:AA

Triggers anabolic processes stimulating growth and reproduction

Question 6

How does dietary restriction affect lifespan?

Answer 6

Dietary restriction and drugs/mutations that alter nutrient sensing pathways show reduced age-related disease

In humans and monkeys DR has been shown to prevent obesity, protect against diabetes, cancer and CVD

Question 7

What does low P:C and high P:C stimulate in the body?

Answer 7

High P:C stimulates TOR, anabolic processes triggers early ageing, early death

Low P:C stimulates AMPk, catabolic processes, life-extending

Excess non protein energy can lead to obesity via insulin resistance

Question 8

Does restriction extant lifespan or does overeating decrease it?

Answer 8

Most studies- restriction from ad lib feeding increases healthy lifespan

Effects of restriction can depend on diet- when maximised for health and longevity no effect of CR may be seen

Question 9

Is it a restriction of protein that extends longevity?

Answer 9

Evidence from insects and mice that restriction of protein and possibly specific amino acids, rather than energy per se responsible for extended lifespan