Theories of ageing Flashcards
(44 cards)
1
Q
Why do we age?
A
- not sure
- over 200 theories of ageing
2
Q
The theories are split up into 3 broad categories. What are they?
A
- wear and tear
- adaptive evolutionary
- non-adaptive evolutionary
3
Q
What is wear and tear?
A
with time, damage is accumulated and the body wears out
4
Q
How are elephants an example of wear and tear?
A
- elephants have 26 teeth:
- 2 tusks, and 6 sets of 4
- when an elephant chews, it uses a set of 4
- when this falls flat, it uses the next set of 4
- as the sets fall out, elephant cant chew grass anymore
- dies of malnutrition
5
Q
Which animals can oppose wear and tear?
A
- sea anemones
- dont seem to age
- they die through disease or getting eaten
- they can repair the intrinsic damage of life at the same rate as it occurs
6
Q
can humans repair any cells?
A
- can repair germline (Cells that become eggs and sperm)
7
Q
Which animal can repair the whole self?
A
- salamanders can repaid a whole limb as the DNA contains a template for rebuilding anything
8
Q
What does adaptive evolutionary suggest?
A
- evolved to age
- Evolution
- natural selection
- if this theory is right, it means ageing should be advantageous
9
Q
Does this theory work?
A
NO
10
Q
Why does this theory not work?
A
- bc it is an advantage for the whole population
- dying old people educe competition for the youth
- for something to be an evolutionary advantage, it must be advantage for individual
11
Q
What is the non- adaptive evolutionary concept?
A
- ageing has come about as a consequence of other characteristics that have been selected for through natural selection
12
Q
What are the 3 parts of the non-adaptive evolutionary theory?
A
- mutation accumulation theory
- antagonistic pleiotropic genes theory
- disposable soma theory
13
Q
What is the mutation accumulation theory?
A
- power of natural selection declines with age
- gene from before reproduction is passed on (early on in life
- if gene expressed after reproduction= cant pass on
- ageing is bc of collection of late acting deleterious genes (causing harm)
- cant get rid off through natural selection (Cant pass on)
- this theory makes sense but there is nor experimental proof
14
Q
What is antagonistic pleiotropic gene theory about?
A
- genes with 2 diff effects= good and bad
- if a gene had an early good effect, but bad late effect= good effect is passed on in gene, but bad effect contributes to ageing
- some experimental proof
- famous study= DROSOPHILA FRUIT FLY
15
Q
Explain the study on drosophila fruit fly
A
- if fruit flies have the aa (abnormal abdomen) allele
- it increases early fertility
- reduces longevity (survival)
- if you make the drosophila flies breed late in life over 15 generations, lifespan extended by 1/3
- but they were short winged and had less flying ability
16
Q
What is the disposable soma theory?
A
- a mathematical model
- come out from the antagonistic pleiotropic gene theory
- views an organism as a machine that transfers free energy into progeny (off spring)
- successful mating is to ensure that genes survive in the most efficient way
17
Q
How does the disposable soma theory model work?
A
- organism can take in a certain amount of energy
- energy used in different ways
= to process the food which is vital
= look for food
= defend
= reproduce
18
Q
Give an example of the soma theory model
A
MICE:
- lets say mouse puts lot of energy to maintain itself
- it wants to live long
- wants to reproduce later
- if a cat eats all the mice
- they did not reproduce
- so species is eradicated
- so if the mouse wants to succeed it needs to breed early and produce lots of offspring to maintain genes
19
Q
What does the soma theory model state then?
A
- the amount of energy expended on maintaining itself and reproducing will depend on the best strategy the species can use to fit into its niche (its part in the environment)
- some animals need to prioritize fertility, whilst other need to prioritize maintenance depending on how high up they are on the food chain
20
Q
How can you look at the soma theory model from thermodynamics view?
A
- 2nd law of thermodynamics states that entropy increases (entropy is chaos, and disorderliness)
- so humans age and decay into disorderliness (humans are normally very ordered and structured)
- humans put energy into defensive and repair mechanisms
- so the rate of ageing depends on how much energy used in defense and maintenance
21
Q
How do we age?
A
4 theories:
- system level theories
- cellular/molecular theories
- genetic theories
- genomic stability
22
Q
What are the theories based on system?
A
- The neuroendocrine theory
23
Q
what does the HPA control?
A
- growth
- development
- not ageing
24
Q
What happens related to the HPA axis that causes ageing?
A
- functional decrease in neurones
- decrease in hormones
- RELATING TO HPA axis
25
What is the evidence that neurones and hormones releated to the HPA axis declines?
- in rats
- pulsatility in GH secretion reduces with age
- becomes less pulsatile and more constant
- when rat has hypothesectomy is done (removal of pituitary gland) and the hormones are replaced= it increased the lifespan of the rat
- bc hormones were being given in pulsatile way
26
What are Cellular/Molecular Level Theories?
- Wear and tear and rate of living
- Cross link formation
- Heat shock proteins
- Hayflick phenomena
27
Describe wear and tear
- mammals have high metabolic rate
- more damage accumulates
- can die earlier
28
Describe cross link formation
- collagen in young person not many cross links
- older person more cross links
- changes properties of soft tissue
- doesn't stretch as well
29
Describe heat shock proteins
- produced at times of stress
- important to disassembling proteins, transporting new proteins
- older age = less heat shock proteins produced
- medically this can be seen, after surgery an older person’s scar is much neater than a younger person’s
- this is bc not enough transport of proteins by heat shock in older people so less fibrous tissue is laid down
- scar in older people is weaker than scar in younger
30
What happens if you have less heat shock proteins?
less ability for cells to deal with stress
31
Who is hayflick? What did he do?
- scientis
- did experiment:
1. took fibroblasts and grew them in culture
2. fibroblasts could only divide a set number of times then they do not divide any more
3. fibroblasts from younger source= more divisions compared to older sources
4. repeat in other cell types
5. came up with idea there is biological clock
6. this allowed cells to divide certain number of times= lead to ageing and death
32
What was the purpose of the body clock?
- he took HeLa cell line in breast cancer
- saw it had unlimited divisions
- was thought that this biological clock was in place to prevent cancer cells from multiplying and getting out of control
33
What are the 2 types of genes that have been identified in humans?
- geronto genes- if we have these, we age faster
| - longevity assurance genes- if we have these, we live longer
34
What studies have taken place to show genes influence ageing?
- twin studies
= monozygotic more likely to livie similar length than dizygotic
= closer tenetically, more similar lifespan
- certain long lived families
= if grandparents live till 90s, you have good chance
- species specific longevity
= one species will live much longer than the other even though their cellular biology is similar
35
What are the studies done on to prove this?
- genes in drosophila, yeast, and nematodes
- bc the genes can shorten and lengthen life
- use species bc they have short life and reproduce quickly
- nematodes have a particular mutation that almost doubles their lifespan
- mutation leadsto an increase in something called superoxide dismutase
36
What are telomeres
- short DNA base sequences at the tail of chromosomes
37
What do telomeres do?
- stabilise the chromosome during cell division
- these shorten with each division of the cell
- once they reach a critical length, no further divisions can occur
- this is the explanation of Hayflick limit
38
What does telomerase do?
- allows the re-expansion of the telomere
39
Where are telomerases found?
- germ cells
| - tumor cells
40
What study was done on men with low risk biopsy prostate cancer?
- on men with low risk biopsy proven prostate cancer
- men were asked to make changes to their lifestyle (diet, activity, stress management, and social support)
- seen that these people had an increase in their telomere length
- and reduction in telomerase activity (which is normal in humans)
- showed that reducing the stress in the environment led to an increase in telomere length and a lesser decrease in telomerase activity
41
What can telomeres do to have an effect on ageing?
- telomere length alters gene expression (ISG15 gene)
- as telomere length shortens, there may be changes in expression of genes and thus the properties of cells leading to some properties of ageing
42
What can turn a cell into a senescence cell?
- DNA damage
- dysfunctional telomeres
- oxidative stress
- strong mitogenic signals
- chromatin perturbations
43
What is a senescent cell?
- arrested growth (DOESNT GROW)
- altered gene expression
- upregulation of genes controlling extracellular matrix degrading enzymes, inflammatory cytokinesand growth factor
- resistant to apoptosis
- disrupt normal tissue structure and function, and stimulate growth of pre-malignant cells
44
What is selfmaintainence done by?
DNA repair−heat shock proteins−protective enzymes−free radical scavengers−longevity assurance genes
