Aging

Question 1

The hallmarks of aging:

Hallmark: Loss of Proteostasis

Answer 1

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

Question 2

Oxidative stress, heat shock, and ER stress causes a folded protein to _____.

Answer 2

unfold

Question 3

The unfolded protein has four pathways it can follow:

Answer 3

1) autophagy: macrophagy within a lysosome or by chaperone mediated-autophagy withing a lysosome
2) proteosomal degradation with ubiquinone
3) Chaperone mediated folding with HSF-1 –> HSP
4) Aggregation of unfolded proteins –> aging

Question 4

Two forms of Alzheimer’s disease:

Note: Alzheimer’s is a loss of proteostasis

Answer 4

1) Rare early onset familial form (fAD) - mutations
2)Much more common, later sporadic form (sAD) (>65
years)

Question 5

What genes and proteins have been found to correlate with AD (Alzheimer’s disease?)

Answer 5

-Proteins correlated: the hypothesis is that Aβ-secretase production/aggregation is the
driving force for AD. These enzymes cleave proteins at different locations depending on the type. APP & CTFβ are transmembrane proteins cleaved by these enzymes
-genes correlated: (Apolipoprotein E (APOE) APOE4 allele (sAD) and • Presenilin 1 & 2 (PSEN1, 2) (fAD)

Question 6

What does the genes and proteins correlated with AD have to say about the mechanism?

Answer 6

The aggregation of Beta-amyloid plaques created by the secretase enzymes that cleave, causes impairment of brain function.

Question 7

What is the Hayflick limit? (cellular senescence)

Answer 7

the discovery that cells divide for a certain amount of time and then senesce (deteriorate) due to telomere attrition (wear) which is caused by a lack of telomerase

Question 8

the caps at the end of each strand of DNA that protect our chromosomes from deterioration or from fusing with neighboring chromosomes.

Answer 8

telomeres

Question 9

Telomeres solve the end replication problem because

Answer 9

the ends of eukaryotic chromosomes were once mistakened for damaged or broken DNA and must therefore thought to be protected from cellular DNA damage response pathways. It was found that these sequences are telomeres that are just becoming shorter the more you replicate due to a lack of telomerase over time.

Question 10

Mechanism of telomerase

Answer 10

adds the polynucleotide “TTAGGG” to the 3’ end of telomeres. It thus reverses telomere shortening. It is a reverse transcriptase mechanism.

Question 11

• Caloric (Dietary) restriction reduces rate of aging; what are the pathways involved?

Answer 11

• Pathways involving IGF & insulin

* Pathway with SIRT1

Question 12

Telomerase is associated with _______ and is found in ____ cells and ______ cells.

Answer 12

• Associated RNA

* In germ cells and cancer cells

Question 13

a term indicating that aged organisms

have a chronic state of inflammation

Answer 13

Inflammaging

Question 14

Amyloid plaques are

Answer 14

Neurofibrallary tangles

Question 15

high AMP – AMPK

high NAD+ - SIRT1

Answer 15

high AMP – AMPK = aging

high NAD+ - SIRT1 = aging

Question 16

genetic diseases with premature aging (genetic instability)

Answer 16

Progeroid syndromes

Question 17

Mutations in what causes progerias?

Answer 17

mutations in DNA
helicases involved in repair
and
mutation in prelamin A

Question 18

DNA repair activity correlates

with ______.

Answer 18

longevity

Question 19

Free radical theory of aging:

Answer 19

states that organisms age because cells accumulate free radical damage over time (free radicals attack proteins and DNA)

Question 20

Evidence against the Free radical theory of aging:

Answer 20

In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan