A&S300	Spring 2006						Name:
Exam 2

You may NOT use any books, notes, or related materials to complete this exam.  
Give brief answers!

1. (2pts) Give two genes that have alleles or polymorphisms that are associated with longevity in humans.

2a. (2 pts)  What does the acronym AGEs stand for and what are AGEs?

2b. (2pts)  Describe the role of AGEs in the aging process.

3. DNA damage theory of aging.
3a. (2pts)  Name two causes of cellular DNA damage.

3b. (1pt) Is the rate at which DNA damage occurs higher in mammals with short or long lifespans? (circle one)

3c. (1 pt) Is the rate of DNA repair higher in mammals with short or long lifespans? (circle one)

4a. (2 pts) What properties of free radicals make them damaging to cells?

4b. (3 pts) Describe cellular defenses against free radicals.

5. (2 pts) Why does the mitochondria play a central role in free radical/oxidative stress theories of aging?

6a. (1 pt)  Define caloric restriction.

6b. (2pts) Caloric restriction extends lifespan in many model systems.  Describe other aspects of the caloric restriction phenotype, that is, the cellular or physiological effects of caloric restriction.

7. (3 pts) Insulin-like signaling pathway.  A, B, and C below point to proteins in this pathway.  Provide gene names or functional assignments.
A.

B.

C. 

Cell membrane

PI(4,5)P2

PI(3,4,5)P3

Nucleus          

DNA

A.

B.

C.

8. (2 pts) In the figure below from Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993 Dec 2;366(6454):461-4 the open squares are wild type.  Which curve is daf-2 and which curve is daf-16?  I realize that the filled diamonds and filled triangles are indistinguishable and either is acceptable as an answer.

daf-2:

daf-16:

9. (2 pts) In addition to lifespan extension, what are the other effects of activation of the insulin-like signaling pathway?

10. (1 pt)  What is molecular function of the SIR2/SIR-2.1/SIRT protein?

11. (1 pt)  What is the effect of raising SIR2/SIR-2.1/SIRT levels in one of these organisms?  Pick an organism and describe the phenotype.

12. (3 pts) What is the Hayflick limit and what do telomeres have to do with it?