Lecture 9

Question 1

What is senescence?

Answer 1

Refers to the increased impairment of physiological function with age

Question 2

What is the relationship between aging and reproduction?

Answer 2

Aging is typically only seen after reproductive maturation

Question 3

What is unique about hydras ability to age?

Answer 3

These reproduce by budding and may not age as their stem cells have an indefinite capacity for self renewal. The transcription factor, forkhead box O is a critical driver in the lack of ageing

Question 4

What is aging?

Answer 4

The mixture of lifespan and senescence

Question 5

What is the definition of lifespan?

Answer 5

The maximum number of years one can live, this is a species characteristic and defined by the longest lived member of the species

Question 6

What appears to determine lifespan?

Answer 6

Genetics although it can be modulated by altering genes or diet

Question 7

What is the difference between life span and life expectancy?

Answer 7

Life span is the maximum possible number of years someone can live while life expectancy is the time an individual can expect to live

Question 8

What is the definition of life expectancy?

Answer 8

The age at which half the population still survives

Question 9

What is the difference between the changes of lifespan and life expectancy in humans?

Answer 9

The lifespan of humans is unlikely to have changed for the past 100,000 years while the life expectancy has dramatically increased due to the development of highly effective treatments for infectious disease

Question 10

What are the theories for the causes of aging?

Answer 10

The wear and tear theories which assume that Aging is a random process which is a result of diminishing energy to repair available to repair damage

Question 11

What is the DNA damage wear and tear theory for the cause of aging?

Answer 11

As an organism gets older DNA damage increases and the efficiency of the enzymes coded by the genes decreases

Question 12

What evidence backs up the idea that DNA damage can cause aging?

Answer 12

Defects in genes encoding DNA repair enzymes can produce premature ageing syndrome in humans

Question 13

What is the oxidative damage wear and tear theory for the cause of aging?

Answer 13

Aging is a by product of normal metabolism where reactive oxygen species such as the superoxide ion and the hydroxyl free radical in peroxide are produced by the mitochondria during metabolism these have the capacity to damage cell membranes, proteins and nucleic acids

Question 14

What evidence backs up the idea that oxidative damage can cause aging?

Answer 14

When drosophila enzymes catalase and superoxide disumtase are overexpressed the lifespan increases 30 to 40%
This evidence isn’t as clear in mammals but caloric restriction does slow aging and this may be due to a reduction in reactive oxygen species levels

Question 15

What is the mitochondiral genome damage theory for aging?

Answer 15

Mitochondrial mutations could lead to defects in energy production, production of reactive oxygen species or induction of apoptosis causing aging

Question 16

What is the random epigenetic drift theory of aging?

Answer 16

There are chance errors made by DNA methylating and demethylating enzymes. Methylating enzymes are more prone to errors leading to a gradual increase in incorrect methylations. there is a correlation between age and the amount of methylation

Question 17

What are the genes involved in aging?

Answer 17

DNA repair genes
insulin signalling
mTOR signalling
chromatin signalling

Question 17

What is the disposable soma theory?

Answer 17

Not a wear and tear theory, based off the fact that the ageing process seems to accelerate after reproduction
It sates that natural selection tunes the life history of an organism so that sufficient resources are invested in maintaining repair mechanisms at least until after the organism has reproduced

Question 17

What are the genes involved in aging?

Answer 17

DNA repair genes
insulin signalling
mTOR signalling
chromatin signalling

Question 18

How are telomeres linked to aging?

Answer 18

Telomeres shorten by about 50 base pairs at each division as DNA polymerase cannot replicate the ends of linear DNA
In the absence of telomerase to offset the shortening of the telomeres cells have a limited number of proliferations known as the hayflick limit
most somatic cells lack telomerase

Question 18

How are telomeres linked to aging?

Answer 18

Telomeres shorten by about 50 base pairs at each division as DNA polymerase cannot replicate the ends of linear DNA
In the absence of telomerase to offset the shortening of the telomeres cells have a limited number of proliferations known as the hayflick limit
most somatic cells lack telomerase

Question 19

What is the structure of telomeric DNA?

Answer 19

vertebrate telomeres are made of a hexameric repeat which is largely double stranded but has a 3’ single stranded overhang

Question 19

What is the structure of telomeric DNA?

Answer 19

vertebrate telomeres are made of a hexameric repeat which is largely double stranded but has a 3’ single stranded overhang

Question 20

What is the function of telomerase?

Answer 20

The RNA of the telomerase binds to the single stranded overhang of the telomere generating a primer for its reverse transcriptase and new telomere sequence is produced in the 5’ to 3’ direction on the parental strand
this elongation is folllowed by a translocation of the RNA allowing repetition of the process
the gap in the lagging strand can then be filled by a DNA polymerase

Question 20

What is the function of telomerase?

Answer 20

The RNA of the telomerase binds to the single stranded overhang of the telomere generating a primer for its reverse transcriptase and new telomere sequence is produced in the 5’ to 3’ direction on the parental strand
this elongation is folllowed by a translocation of the RNA allowing repetition of the process
the gap in the lagging strand can then be filled by a DNA polymerase

Question 21

What is the structure of telomerase?

Answer 21

It is a complex of proteins including reverse transcriptase and an RNA that acts as a template for catalyzing DNA addition at the telomere

Question 21

What is the structure of telomerase?

Answer 21

It is a complex of proteins including reverse transcriptase and an RNA that acts as a template for catalyzing DNA addition at the telomere

Question 22

What is the evidence which might suggest that telomeres do not affect aging?

Answer 22

There is no correlation between lifespan and telomere length, however there is evidence to suggest that individuals with longer telomeres will live longer

Question 22

What is the evidence which might suggest that telomeres do not affect aging?

Answer 22

There is no correlation between lifespan and telomere length, however there is evidence to suggest that individuals with longer telomeres will live longer

Question 23

What is Hutchinson-Gilford Progeria syndrome?

Answer 23

An autosomal dominant condition caused by a de novo mutation in the lamin A/C gene which are filament proteins of the nuclear scaffold which causes the nuclear envelope to be unstable causing progressive damage to the structure and function of the nucleus
this causes accelerated aging with an average life expectancy of 13 years and most individuals dying from cardiac abnormalities

Question 23

What is Hutchinson-Gilford Progeria syndrome?

Answer 23

An autosomal dominant condition caused by a de novo mutation in the lamin A/C gene which are filament proteins of the nuclear scaffold which causes the nuclear envelope to be unstable causing progressive damage to the structure and function of the nucleus
this causes accelerated aging with an average life expectancy of 13 years and most individuals dying from cardiac abnormalities

Question 24

What is werner’s syndrome?

Answer 24

An autosomal recessive disorder which has its onset in the second decade of life, the mutated gene codes for a 3’ to 5’ DNA helicase which can also act as 3’ to 5’ exonuclease activity and can act as a transcriptional activator. Telomeres of these individuals shorten faster causing the individuals to age rapidly and usually die before 50 from cancer or vascular disease

Question 24

What is werner’s syndrome?

Answer 24

An autosomal recessive disorder which has its onset in the second decade of life, the mutated gene codes for a 3’ to 5’ DNA helicase which can also act as 3’ to 5’ exonuclease activity and can act as a transcriptional activator. Telomeres of these individuals shorten faster causing the individuals to age rapidly and usually die before 50 from cancer or vascular disease

Question 25

How has insulin signalling been linked to aging?

Answer 25

The dauer stage which the C. Elegans can go into is induced by knocking out of the insulin homolog receptor, a less severe knock out resulted in the adults living 4 times longer. This was coupled with an increase in DNA repair enzymes, enzymes that protect against reactive oxygen species and the foxo transcription factor.
There are similar effects conserved throughout the animal kingdom

Question 25

How has insulin signalling been linked to aging?

Answer 25

The dauer stage which the C. Elegans can go into is induced by knocking out of the insulin homolog receptor, a less severe knock out resulted in the adults living 4 times longer. This was coupled with an increase in DNA repair enzymes, enzymes that protect against reactive oxygen species and the foxo transcription factor.
There are similar effects conserved throughout the animal kingdom

Question 26

How is the mTOR pathway linked to aging?

Answer 26

Linked to the insulin pathway with high levels of insulin leading to high levels of mTORC1 activity
Mice with lower levels of mTORC1 lived longer, had less age related cognitive dysfunction, more functional stem cells and increased autophagy

Question 26

How is the mTOR pathway linked to aging?

Answer 26

Linked to the insulin pathway with high levels of insulin leading to high levels of mTORC1 activity
Mice with lower levels of mTORC1 lived longer, had less age related cognitive dysfunction, more functional stem cells and increased autophagy

Question 27

How is chromatin remodeling linked to aging?

Answer 27

Sirtuin genes encode histone deacetylation genes which have the typical function of silencing chromatin, they also repair chromatin breaks

Question 27

How is chromatin remodeling linked to aging?

Answer 27

Sirtuin genes encode histone deacetylation genes which have the typical function of silencing chromatin, they also repair chromatin breaks
As we age we experience more double stranded DNA breaks, this could result in the genes being to busy repairing these to control gene expression resulting in inappropriate genes being expressed

Question 28

What experiments have been done to suggest the sirtuin genes may play a role in aging?

Answer 28

Resveratol found in red wine can boost SRT1 levels which has been found to boost yeast life span
Mice which are knockouts for SIRT6 die very young, however if the gene is over expressed instead then males live 15% longer

Question 29

What can allow cells to surpass the hayflick limit in culture?

Answer 29

inactivation of tumour suppressor genes such as p53 and Rb by viral protein oncoproteins causing cells to lead an extended life span until the telomeres are critically shortened known as mortality stage 2