Lecture 19

Question 1

Why Do We Age

Answer 1

“It’s in our genes”
Genetic variation in ‘longevity’ genes
may influence lifespan

Question 2

what are Single Nucleotide Polymorphisms (SNPs)

Answer 2

Each SNP represents a difference in a single DNA building block (nucleotide). They are responsible for human genetic variation

Question 3

SNP frequency

Answer 3

10 million SNPs within the human population
– 1 every 300 nucleotides

Most frequent source for polymorphic changes

Not the only source of genetic variation

But represents major source that distinguishes one individual from another

Question 4

Nutritional Genomics

Answer 4

certain factors can improve, impair or have no effect on ones performance. Eg. caffeine on athletic performance. metabolize slowly, quickly or moderately.

Question 5

Nutritional Genomics cause

Answer 5

wide variability in nutritional data. some interventions work much better on some people or do not work at all

Question 6

HapMap project is

Answer 6

a database that catalogues the 10 million SNPs
identified in the human genome

Question 7

in hapmap database…

Answer 7

Genes are identified in green, SNPs are identified by blue lines. Number of SNPs in a single chromosome is so dense
that you have a solid blue bar.

Question 8

Aging is associated with

Answer 8

an increase in inflammatory
cytokines that contribute to various age-related disorders

Question 9

some examples of age related disorder

Answer 9

Alzheimer’s, cardiovascular disease, arthritis

Question 10

Plasma levels of Interleukin-6 (IL-6) is an inflammatory cytokine is positively correlated with

Answer 10

greater mortality

Question 11

SNP in the promoter* of IL-6 is associated with

Answer 11

increased IL-6 and
an increased mortality rate

Question 12

Polymorphism:

Answer 12

a DNA sequence variation that is common in the population

Question 13

a promoter is a

Answer 13

region of DNA that initiates transcription of a particular gene

Question 14

Damage to the mitochondrial genome occurs

Answer 14

10x more frequently than the nuclear genome. Due to the generation of reactive oxygen species (ROS)

Question 15

reactive oxygen species (ROS) are

Answer 15

Highly reactive chemical species containing oxygen

Question 16

reactive oxygen species (ROS) examples

Answer 16

Peroxides
Superoxide
Hydroxyl radical
Singlet oxygen

Question 17

DNA polymerase
gamma:

Answer 17

replicates and proof reads / repairs mitochondrial DNA

Question 18

Accumulating mutations in mitochondrial DNA

Answer 18

accelerate
aging

Question 19

Errors in replication become

Answer 19

more frequent as we age

Question 20

With aging, DNA polymerase gamma

Answer 20

corrects errors less effectively

Question 21

more apoptosis and reactive o2 species is a

Answer 21

side effect of aging

Question 22

what does DNA polymerase gamma do

Answer 22

replicates and proof
reads / repairs mitochondrial DNA

Question 23

in mice genetically engineered to carry
mutations in mitochondrial (mt) DNA
polymerase γ (gamma) the results are:

Answer 23

• mt DNA replication is error-prone
• Proof-reading activity is lost!
• Mice show accelerated signs of aging evident by 25 weeks (young
  adult stage) weight loss, hair loss, curvature of spine; reduced lifespan

Question 24

The mutated mice show a

Answer 24

Causative link between mtDNA mutations and aging phenotype

Question 25

Can excersize reduce effects of aging?

Answer 25

yes, aging is Inevitable
But healthy aging can be influenced by
lifestyle choices

Question 26

what is caloric Restriction

Answer 26

Generally refers to a 20 to 40% reduction in daily energy intake, but without malnutrition

Question 27

Caloric restriction extended

Answer 27

healthy lifespan in rats, yeast, worms, fruit flies, mice, rabbits, dogs, and monkeys (no conclusive evidence in humans)

Question 28

Study on how does EXERCISE compare to
drugs that are used to improve the
ability of muscle to respond to insulin
(i.e. insulin sensitivity)?

Answer 28

3234 diabetes-prone participants (diagnosed with prediabetes)
studied over 4 years
2 groups:
1) metformin (given as a preventative drug)
2) lifestyle modification

What were the lifestyle recommendations?
150 min per week of moderate exercise
Encouraged to follow Food Pyramid - this is a US study!
Target was to lose ~7% of initial body weight

Question 29

findings of how does EXERCISE compare to
drugs that are used to improve the ability of muscle to respond to insulin (i.e. insulin sensitivity)?

Answer 29

Incidence of diabetes blunted the best by
lifestyle intervention. 31% with drug, 58% lifestyle reduction