Cellular Aging

Question 1

Cellular aging is regulated by?

Answer 1

Genes that are evolutionarily conserved from yeast to worms to mammals.

Question 2

Briefly outline the process behind cellular aging

Answer 2

Genetic abnormalities and accumulation of cellular and molecular damage due to exogenous influences cause a progressive decline in cellular function and viability.

Question 3

Several mechanisms, some ____ _______ and others _________ _________ are believed to play a role in aging.

Answer 3

Cell intrinsic

Environmentally induced

Question 4

What 4 mechanisms play a role in cellular aging?

Answer 4

1. DNA damage
2. Cellular scenescence
3. Defective protein homeostasis
4. Deregulated nutrient sensing

Question 5

How many new mutations per year is the average haemopoietic stem cell expected to suffer?

Answer 5

14

Question 6

Patients with Werner syndrome show premature aging due to a defective DNA ______. This causes rapid _______ of _______ damage that may mimic the injury that normally accumulates during cellular _______.

Answer 6

Helicase
Accumulation
Chromosomal
Aging

Question 7

Other disorders in which patients display some of the manifestations of aging at an increased rate.

Answer 7

Bloom syndrome

Ataxia-telangiectasia

Question 8

In Bloom syndrome and Ataxia-Telangiectasia, mutated genes encode proteins involved in?

Answer 8

Repairing double-strand breaks in DNA

Question 9

All normal cells have a limited capacity for?

Answer 9

Replication

Question 10

After a _______ number of divisions, cells become __________ in a terminally __-______ state, known as ________ ______.

Answer 10

Fixed
Arrested
Non-dividing
Replicative senesence

Question 11

Aging is associated with

Answer 11

progressive replicative senescence of cells.

Question 12

T or F: Cells from children can undergo fewer rounds of replication than cells of older people.

Answer 12

False

Question 13

What are the 2 mechanisms underlying cellular senescence?

Answer 13

1. Telomere attrition

2. Activation of tumour suppressor genes

Question 14

What are telomeres?

Answer 14

Short repeated sequences of DNA present at the ends of linear chromosomes

Question 15

What are telomeres important for?

Answer 15

1. Ensuring complete replication of chromosome ends

2. Protecting the ends from fusion and degradation

Question 16

What happens to telomeres as somatic cell replication occurs?

Answer 16

A small section of the telomere is not duplicated each time and telomeres become progressively short.

Question 17

What is the consequence of telomere shortening?

Answer 17

The ends of the chromosomes are no longer protected and are seen as broken DNA, signalling cell cycle arrest

Question 18

How is telomere length maintained?

Answer 18

Nucleotide addition mediated by an enzyme called telomerase

Question 19

What is telomerase?

Answer 19

A specialised RNA-protein complex that uses its own RNA as a template for adding nucleotides to the ends of chromosomes.

Question 20

Telomerase activity is expressed in which cells?

Answer 20

Germ cells
Stem cells (low level)

Question 21

Telomerase activity is absent in which cells?

Answer 21

Most somatic tissues

Question 22

Therefore, as most somatic cells age, their telomeres become shorter and they exit the cell cycle. This results in?

Answer 22

An inability to generate new cells to replace damaged ones.

Question 23

In immortalised cancer cells, telomerase is usually _______ and telomere length is __________.

Answer 23

Reactivated

Stabilised

Question 24

What diseases has premature telomere shortening been associated with?

Answer 24

Pulmonary fibrosis

Aplastic anaemia

Question 25

Which tumour suppressor genes are correlated with chronologic age?

Answer 25

p16 | INK4a

Question 26

Where are p16 and INK4a located?

Answer 26

CDKNA2A locus

Question 27

What does p16 do?

Answer 27

Controlling G1 to S phase progression during the cell cycle.

Question 28

What does p16 protect the cell from?

Answer 28

Uncontrolled mitogenic signales

Question 29

Protein homeostasis involves 2 mechanisms.

Answer 29

1. Maintenance of proteins in their correctly folded conformations 2. Degradation of misfolded proteins by the autophagy-lysosome system and ubiquitin-proteasome system

Question 30

Maintenance of protein conformation is mediated by?

Answer 30

Chaperones eg heat shock protein family

Question 31

What is rapamycin?

Answer 31

mTOR inhibitor

Question 32

What role does rapamycin play in cellular aging?

Answer 32

Promotes autophagy that probably prevents accumulation of misfolded proteins which would otherwise trigger apoptosis.

Question 33

T or F: caloric restriction decreases longevity.

Answer 33

False

Question 34

2 pathways by which caloric restriction may increase longevity

Answer 34

1. Reducing signaling intensity of IGF-1 pathway | 2. Increasing sirtuins

Question 35

What role does IGF-1 play in cellular aging?

Answer 35

IGF-1 informs cells of the availability of glucose, promoting an anabolic state as well as cell growth and replication, via multiple downstream targets, the 2 most pertinent being AKT and its downstream target, mTOR

Question 36

What is IGF-1?

Answer 36

Produced by many cell types in response to growth hormone secretion by the pituitary, mimics intracellular signaling by insulin.

Question 37

What are sirtuins?

Answer 37

A family of NAD-dependent protein deacetylases.

Question 38

How many types of sirtuins are there?

Answer 38

At least 7 type in different cellular compartments with non-redundant functions.

Question 39

What are the functions of sirtuins?

Answer 39

Adapt bodily functions to environmental stresses including food deprivation and DNA damage.

Question 40

What role do sirtuins have in cellular aging?

Answer 40

Promote the expression of several genes whose products increase longevity.

Question 41

What are the actions of proteins produced by sirtuins?

Answer 41

Inhibit metabolic activity Reduce apoptosis Stimulate protein folding Inhibit harmful effects of oxygen free radicals Increase insulin sensitivity and glucose metabolism