Final Exam Flashcards

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1
Q

Nematode Aging

A

LET-363 and Target of rapamycin promote aging

Daf-2 and insulin/IGF-1 receptor to daf-16/FOXO stop aging

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2
Q

Fruit Fly Aging

A

Target of rapamycin promotes aging

dINR and insulin/IGF-1 receptor to dFOXO stop aging

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3
Q

Mouse Aging

A

Target of rapamycin promotes aging

Growth of hormone to IGF-1, IGF-1 receptor and insulin receptor to FOXO1 and FOXO3 stop aging

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4
Q

RNA interference (RNAi)

A

Post-transcription gene silencing; double-stranded RNA (when introduced into a cell) causes sequencing-specific degradation of homologous mRNA sequences

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5
Q

Argonaute

A

One of the main components in RISC; cleaves and discards the passenger strand of the siRNA duplex leading to activation of the RISC

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6
Q

Dicer

A

RNAase 3 enzyme

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7
Q

siRNA

A

21-23 nt short interfering RNA

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8
Q

RISC

A

RNA-inducing silencing complex

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9
Q

ER stress

A

Physiological and pathological stimuli disrupt the ER homeostasis, resulting in midfielder and unfolded proteins

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10
Q

Unfolded Protein Response (UPR)

A

ER stress activated complex signaling network to reduce ER stress and restore the ER homeostasis

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11
Q

Three aims of UPR

A

1) restore normal function of cell by stopping protein translation
2) degrading midfielder proteins
3) activating signaling pathways that increase the production of molecular chaperones in protein folding

If not achieved, UPR aims towards apoptosis

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12
Q

BIP

A

Immunoglobin biding protein

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13
Q

ATF6

A

Activating Transcription Factor 6

Not required for longevity phenotype of daf-2 mutants

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14
Q

XBP1

A

X-box binding protein 1

New ER stress response, longevity genes leads to improved ER homeostasis

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15
Q

PERK

A

PKR-like ER kinase

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16
Q

IRE1

A

Inositol Requiring 1

Required for longevity phenotype of daf-2 mutants

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17
Q

ERAD

A

ER-associated protein degradation

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18
Q

Pek-1

A

Not required for longevity phenotype of daf-2 mutants

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19
Q

Sir-2 and daf-16

A

Sir2 stimulates daf-16 activity to increase worm survival

14-3-3 and sir2 are required for daf-16 to function

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20
Q

RAS Signal Pathway components

A

SOS, GAP, ERK, RAF, MEK, FOS

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21
Q

SOS

A

Guanine nucleotide exchange factor (first in pathway)

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22
Q

GAP

A

GTPase activating protein (after SOS)

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23
Q

ERK

A

Extracellular signal-regulated kinases

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24
Q

RAF, MEK, ERK

A

Protein kinase phosphorilation cascade (follows GAP)

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25
Q

FOS

A

Transcription factor

Cell proliferation, differentiation, and survival (end of pathway)

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26
Q

Inhibition of RAS

A

Extends fly lifespan

RAS dominate negative mutants

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27
Q

MEK inhibitor and what it does

A

Trametinib

Extends fly lifespan

28
Q

Trametinib

A

MEK inhibitor; approved for use with dabrafenib for untraceable/metastatic melanoma with BRAF mutation

29
Q

14-3-3 protein name

A

Name refers to elution and migration pattern of proteins on DEAE-cellulose chromatography and starch-gel electrophoresis

30
Q

14-3-3 ability

A

Ability to bind a multitude of functionally diverse Signaling proteins

Includes kinases, phosphatases, and transmembrane receptors

31
Q

What 14-3-3 does

A

14-3-3 binding variably regulates its partners, ranging from positive to negative regulation via several different mechanisms

Bonds specific phosphoserine/threonine motifs on the target protein

32
Q

14-3-3 First major mode of action

A

binding can alter ability to target protein to interact with other proteins (bind with IRS-1 attenuated ability to recruit and activate PI-3 kinase)

33
Q

14-3-3 second major mode of action

A

Binding can modify the target protein localization which causes its target’s exclusion from the nucleus and it’s retention in the cytoplasm

34
Q

14-3-3 third major mode of action

A

Can bridge two proteins together, serving as a phosphorylation dependent scaffold protein

35
Q

14-3-3 forth major mode of action

A

Binding can alter the intrinsic catalytic activity of the target protein, inhibit or augment it’s function

36
Q

14-3-3 fifth major mode of action

A

Binding can protect the target protein from other modifications such as dephosphorylation and proteolysis

37
Q

Sirtuin (or Sir2 proteins)

A

Sir2 - silent information regulation 2

Required for lifespan extension resulted from glucose restriction in yeast cells

Are protein deacetylases dependent on nicotine adenine dinucleotide (NAD) and are found in organisms ranging from Baxter to humans

Various enzyme activities (mono-ribosyltransferase and deacylase)

38
Q

Overexpression of Sir2

A

Extends lifespan of C. elegans, Drosophila, and mouse

In C. elegans, promotes nuclear localization of DAF-16/FOXO transcription factor

39
Q

Saccharomyces cerevisiae, three different kinds of loci subject to gene silencing

A

Silent mating-type loci, telomeric regions, rDNA repeats

40
Q

Accumulation of rDNA circles; Extrachromosomal rDNA circle (ERC)

A

A young cell — excision/inheritance of ERC — replication, recombination, asymmetrical segregation (can repeat this step) — old cell, nucleolar fragmentation, death

41
Q

Deacylase activity

A

Important for lifespan regulation

Depends on NAD level, which links it’s enzymatic activity directly to energy status of cell via cellular NAD:NADH ratio

42
Q

Nicotinamide adenine dinuleotide (NAD)

A

Extends C. elegans lifespan

43
Q

What does Sirtuins (NAD+ dependent deacetylases) do

A

Remove acetyl groups from lysine residues within proteins in the presence of NAD+

44
Q

Yeast Sir2

A

A histone deacetylase

45
Q

Sir2 enzyme activity results

A

Results in tighter packaging of chromatin and a reduction in transcription at the targeted gene locus: telomeric sequences, the hidden MAT loci (HM loci) and the ribosomal DNA locus

46
Q

Seven sirtuins in mammals

A

Sirt1 - homologous of Sir2, overexpression mimics diet restriction

Sirt2 - mainly expressed in brain

Sirt3, Sirt4, Sirt5 - active in mitochondria

Sirt6 and Sirt7 - active in nucleus of cell

47
Q

Overexpression of sirt6

A

Decreases level of phosphorylated AKT

Decreases level of phosphorylated FOXO and S6K

INCREASES LONGEVITY OF MALE MICE - reduces IGF signaling pathway in white adipose tissue

48
Q

Resveratrol

A

Red wine

49
Q

Sirt1 activator SRT1720

A

Extends lifespan and improves health of mice fed standard diet

50
Q

What does Resveratrol do

A

Improves health and survival of mice in a high-caloric diet

51
Q

Autophagy definition

A

A catabolic process involving degradation of a cell’s own components through the lysosomal machinery

52
Q

Autophagy: first type

A

Chaperone-mediated: a cytosolic chaperone protein recognizes and binds proteins to form a substrate-chaperone complex delivered to the lysosome through lysosome-associated membrane protein (LAMP) type 2A

53
Q

Autophagy: second type

A

Microautophagy: a direct engulfment if cellular components by invagination of the lysosomal member

54
Q

Autophagy: third type

A

Macroautophagy: process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for degradation and recycling of the resulting macromolecules

55
Q

Biological functions of autophagy

A
Survival during starvation
anti-aging
differentiation and development
protection against neurodegeneration
innate immunity
cell growth control/tumor suppression
cell death
56
Q

When does autophagy occur

A

Misfolded protein goes to phagosomes/lysosomes, which goes to autophagy

57
Q

Telomere definition

A

A region of repetitive nucleotide sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes

58
Q

About telomere

A

Shorten with each cell division

Estimated that human telomere lose about 100 base pairs from their telomeric DNA at each mitosis

59
Q

Cellular senescence

A

Triggered when telomere are on average 4-6 kb

60
Q

Telomere Hypothesis of Aging

A

Telomeres shorten with age (tissue with high cell turnover); therefore, telomere shortening is a cause of aging

61
Q

Telomerase definition

A

An enzyme that adds telomere repeat sequences to the 3’ end of DNA strands

Reverse transcriptase that carries its own RNA molecule, used as a template when it elongates telomeres

62
Q

Long telomeric DNA

A

Long lifespan in worms

63
Q

p53

A

Guardian of the genome

Cell cycle arrest — DNA repair — cell cycle restart — cellular and genetic stability

Apoptosis — death and elimination of damaged cells — cellular and genetic stability

64
Q

Progeria / Hutchinson-Gilford Progeria Syndrome (HGPS)

A

Extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age

1 per 8 million live births

Diseased live to mid teens and early twenties; occurs as a new mutation and is rarely inherited

65
Q

Werner syndrome

A

An autosomal recessive disorder. WRN gene associated with this syndrome lies on chromosome 8 and it’s the only gene known to be associated with Werner syndrome.

Caused by mutation in the WRN gene which codes a DNA helicase that functions 3’ to 5’

66
Q

What is observed in Werner syndrome

A

Increase telomere attrition and genomic instability

Rapid telomere decay is thought to play a causal role in the clinical and pathological manifestations of the disease