Molecular hallmarks of ageing 1

Question 1

Ageing

Answer 1

characterised by gradual decline in normal physiological functions and integrity in a time dependent manner which will affect the biological systems e.g., molecular interactions, cellular function and tissue structure and physiological homeostasis.

Question 2

6 diseases associated with ageing

Answer 2

1.arthritis
2.heart disease
3.cancer
4.diabetes
5.COPD
6.asthma.

Question 3

are an individual’s hearing and vision effected by ageing?

Answer 3

Yes cause hearing loss and reduced vision or blindness

Question 4

Life expectancy

Answer 4

average length of time organism is expected to live-80 years

Question 5

Lifespan

Answer 5

max time organism is expected to survive -125 years

Question 6

Health span

Answer 6

percentage of individuals life where they live in good health

Question 7

Biological age

Answer 7

age that determine the health of organs and tissues and cells in an individual

Question 8

3 factors that can effect someones biological age

Answer 8

1.alcohol
2. stress
3. exercise

Question 9

Chronological age

Answer 9

refers to actual amount of time a person is alive

Question 10

primary hallmarks

Answer 10

cause the disease -initiate it and are negative

Question 11

2 examples of primary hallmarks

Answer 11

1.endogenous damage
2.exogenous damage

Question 12

3 things in endogenous damage

Answer 12

replication errors, spontaneous reactions, reactive oxygen species(ROS)

Question 13

what is repair machinery in endogenous damage?

Answer 13

In a young cell there is more repair than damage so the machinery would be good , when older the machinery is not as efficient as there is more damage because there are more mistake and damage to DNA causing genome instability and the machinery is also ageing therefore more mistakes and damage accumulated in cells

Question 14

what is ROS in endogenous damage?

Answer 14

highly reactive molecules therefore have a high ability to bind to DNA and protein and lipids in cells and modify them and change their integrity

Question 15

example of endogenous source(ROS)

Answer 15

mitochondria-produces ADP for cellular process and produces ROS -in the young cells the antioxidant system will clear the ROS remove and detoxify it. When ROS increases the antioxidant is exceeded it won’t be able to remove all the ROS which puts it into oxidative stress so the cells cannot function leading to genome instability.

Question 16

what is the free radical theory?

Answer 16

ageing is caused by accumulation of damage inflicted by ROS

Question 17

what happens to the epigenetic alteration when ageing?

Answer 17

Epigenetic alteration accelerates ageing process. At a young age there are many repetitive sequences -transposable elements which are methylated

Question 18

in epigenetic alteration, what should happen to the transposable elements which are highly methylated

Answer 18

should be suppressed -As an individual grows older they lose methylation pattern-black circles become white circles-global hypermethylation

Question 19

when ageing happens there is global by-methylation, what will this do to the methylation pattern?

Answer 19

loss of methylated pattern and most genes become active

Question 20

what are the misfolding/structural changes of loss of proteostasis ?

Answer 20

The protein needs to be folded properly in order to function and if not, they cannot function and the whole cell cannot function.

Question 21

with ageing what happens when there is a change of loss of proteostasis

Answer 21

quality control system cannot cope with amount of unfolded protein and damage which is accumulated within the cell so there will be more unfolded proteins-protein aggregation

Question 22

secondary hallmark

Answer 22

response to the damage from the primary can be positive or negative -which can damage cells and organs

Question 23

integrative hallmark

Answer 23

physiological changes that can be seen in elderly -links to phenotype in ageing

Question 24

2 things of integrative hallmark

Answer 24

-stem cell exhaustion-no new cell
-altered communication-no coordination

Question 25

antagonistic hallmarks

Answer 25

response to damage caused by primary hallmarks

Question 26

3 examples of antagonist hallmark(response to damage from primary hallmark)

Answer 26

-mitochondria dysfunction-no energy
-deregulated nutrient sensing-reducing nutrient uptake to reduce overload to damaged cells
-cellular senescence -frozen in time

Question 27

Double stand break(DSB)

Answer 27

these in the dna are less in young people and due to age, they increase. Gamma H2AX binds to the cells of the dsb and can be used as biomarker of ageing(senescent cells) and DNA damage

Question 28

Telomere

Answer 28

repetitive nucleotide sequences at the end of chromosomes

Question 29

What is the role of a telomere?

Answer 29

protect the end of chromosomes from decay and fusion with other chromosomes
Seqeunce:AGGGTT

Question 30

how does the cell divided during ageing effect the telomeres

Answer 30

as you age the cell divides, it replicates and there is a loss so telomeres get shorter

Question 31

how do telomeres lead to genomic instability and malfunction in protein of cells

Answer 31

when older the telomeres are 4kb so they are reduced in size and then signal the cell which stops the replication. If the replication is passed it contains the damage in the genetic material.

Question 32

Telomere theory

Answer 32

ageing is caused as a result of replication dependent shortening of telomere that protect the end of chromosomes -genome instability

Question 33

Cancer

Answer 33

multiple replication and abnormal cell. The cancer cell have enzyme telomerase which adds more telomeres at the end of the chromosomes even though they are damaged, allows non division.

Question 34

In methylation what does the white circle represent?

Answer 34

unmethylated

Question 35

in methylation, what does the black circle represent?

Answer 35

methylated

Question 36

Unmethylated

Answer 36

promoters allow transcription factors to bind to promoter, the gene is then transcribed meaning its active

Question 37

Methylated

Answer 37

transcription factor cannot bind to so there is no transcription

Question 38

Tumour suppressor genes

Answer 38

are methylated meaning they are active so they supress tumours

Question 39

if tumour suppressor genes are methylated with age what will this cause?

Answer 39

cancer

Question 40

DNA methyltransferase 1(DNMT1)

Answer 40

enzyme responsible for maintaining DNA methylation pattern as cell divides

Question 41

what is the role of DNMT1?

Answer 41

maintains the pattern ; the enzyme makes sure to copy it every time

Question 42

IN DNMT1, with ageing how is the methylation machinery effected?

Answer 42

With ageing the methylation machinery starts to make mistakes so it doesn’t copy the exact gene before and mistakes will lead to genes switching off or on leading to increased risk of cancer.