Molecular Mechanisms of Aging

Question 1

How can genetics control aging?

Answer 1

Increase resistance to lethal injury, increase ability to respond to nutritional poverty

Single gene mutations (resist ox damage, etc.)
Multiple genes

Question 2

______ is the single strongest risk factor for several diseases.

Answer 2

Aging

Question 3

What are two evolutionary theories as to why we age?

Answer 3

1. Mutation accumulation (mutation producing late life deleterious effects not removed by natural selection - just need to be healthy to procreate)
2. Antagonistic pleiotropy (genes with beneficial effect at young age may have deleterious effect at older age - controlling excessive proliferation to prevent cancer may result in decreased cell repair)

Question 4

What are the hallmarks of aging?

Answer 4

Genomic instability 
Telomere attrition
Epigenetic alterations
Loss of proteostasis
Deregulated nutrient sensing 
Mitochondrial dysfunction
Cellular senescence 
Stem cell exhaustion 
Altered intracellular communication

Question 5

How does free radical damage occur?

Answer 5

Oxygen free radicals highly reactive - bind to:
Lipids - peroxidation
DNA - mutations
Proteins - cross linking

Question 6

Describe glycosylation as it relates to damage and aging.

Answer 6

Non enzymatic attachment of glucose
Advanced glycation endproducts (AGE) 
-protein crosslinking
-DNA damage
Glycation leads to cataracts

Question 7

Major source of energy production and free radicals. (also has independent DNA as a possible program source)

Answer 7

Mitochondria

Question 8

What events can lead to loss of proteostasis and aging?

Answer 8

Heat shock
ER stress
Oxidative stress
Aging when normal protective mechanisms don’t work to fix aggregation

Question 9

What affect does dietary restriction have on aging?

Answer 9

Dietary restriction seems to delay aging

Question 10

_________ regulate protein acetylation by NAD+ dependent deacetylation

Answer 10

Sirtuins
-decrease protein acetylation
-metabolic function
-overall health
(NAD+ repletion enhanced lifespan in mice)
-increase NAD+ to increase sirtuin activity, which blocks aging

Question 11

What is the Hayflick limit?

Answer 11

Cellular senescence
Certain number of population doublings until cells stop dividing
-still alive, but senescent
-dependent on doubling number, not time

Question 12

What is the idea of homeostatic reserve in relation to aging?

Answer 12

Have larger reserve when young
Age reduces reserve
Enough capacity to handle everyday, but then stress can be a problem
Eventually, big challenges not handled well
Then, smaller challenges are not handled well
At the end, imperceptible challenges not handled

Question 13

Goal is to increase _________, not just longevity. Still want to have meaningful functions.

Answer 13

Health span

Chronological age and functional age not the same

Question 14

What have mice experiments shown to reduce aging?

Answer 14

Reduce/eliminate senescent cells
Linking circulations of old and young mice
Extracellular proteins such as GDF11