Molecular hallmarks of ageing 2 Flashcards
how is the mitochondrial intervention helpful?
important for mitochondrial regulation because it uses dynamic system so it separates and mitochondria merges together in process -called fusion. This can provide more ATP.
what is mitochondrial intervention?
known to improve outcome of ageing and ageing associated diseases
what happens to the mitochondria during ageing?
becomes inefficient in producing ATP so it doesn’t produce as much ATP as the cell requires so it will have to work harder.
during ageing the mitochondria has to work harder so ROS is produced , what will this cause?
causing damage to the cells and the antioxidant system increases so it works hard to get rid of the ROS that is generated.
in older age what happens to function of mitochondria?
function of mitochondria declines so it can’t produce enough ATP to provide energy for cellular function and oxidative stress as mitochondria becomes leaky and ROS increases- antioxidant system can’t cope with amount of ROS and the DNA repair machinery is not that efficient.
Cellular system
mitophagy-removes mitochondria that is damaged
why does mitochondrial dysfunction happen?
Dynamic process of mitochondria-need more energy or less , depending on the need of the cell the cell cannot switch between fusions and fission separating the cell or combining to provide more energy
Mitochondrial dynamic
produces ATP and Ros and collects damage to the DNA -in the fission process the mitochondria cuts into 2 the damaged part goes through mitophagy and the healthy part does the process again
Fusion
combine 2 ATP mitochondria or multiple mitochondria-more energy for the cell
what’s happens in fusion during ageing?
cannot get rid of damaged part and there is less energy.
name 3 deregulated nutrient sensing pathways
Biochemical pathways-sense the nutrition status of a cell.
Insulin growth factor 1(IGF1):needs to be regulated -change during different stages of life pathway(IIS)
Several cells produce IGF1 -liver is the most common source-stimulates bone and muscle growth
how is AKT activated
Insulin growth factor ligands bind to its receptor then stimulate a cascade of events which activates secondary messengers
AKT function
protein synthesis, cell survival and cell proliferation needed for growth and development.
what are 4 things ATK does?
-induces inflammation signals and senescence phenotype
-inhibits apoptosis
-inhibits foxo-transcription of genes that are involved in longevity and inhibits stress and resistance and autophagy
Deregulated nutrient sensing pathways
-mTOR pathway
-SIRTs pathway: involved in metabolic pathways such as fat production, insulin secretion, glucose synthesis, mitochondrial biosynthesis, ATP production and autophagy. Certain things such as stress and viral infection can activate this. Once these compounds happen secondary messengers get activated and activates AMPK.
AMPK function
stimulates autophagy -promotes antioxidant system and inhibit ageing
what does the insulin, IGF1 pathway?
1.Autophagy
2.protein synthesis
3.nutrient sensing, mitochondrial function, oxidative stress
Foods that are good for ageing
raspberries -contains resveratrol
Cellular senescence
process that causes premature or permanent proliferation(increases cell numbers by replicating in cell division) on cells. It is aged or older cell
what happens when cells keep replicating in cell division?
hits an intercellular stop sign where telomeres are shortened and damage is caused by ROS then replication is blocked as it communicates it that is has had enough damage and it shouldn’t replicate anymore
Senescent cell
cell accumulated to much damage
Hayflick limit/ Hayflick phenomenon
number of times a cell replicates before it goes into senescence. Once it hits the limit it will stop replicating
in cell division how does cancer deal with the signal given?
cancer cells bypass this signal and keep replicating and growing which leads to tumours
Senescence-associated secretory phenotype (SASP)
mixture of proinflammatory signals and matrix metalloproteinases(MMPs)
what enzyme does senescent cells produce?
SA-B(beta galatctose) gal or SABG
function of SA-B(beta galatctose) gal or SABG
converts galactosides into monosaccharide only in senescent cells
proinflammatory signal
causes inflammation leads to inflammaging, MMps are proteases that can degrade all kinds of extracellular matrix
what is another marker for senescent cells
chi 67- marker of proliferation
primary purpose of antagonistic hallmark or senescence
Due to ageing there is change in senescence. One way this is through is there are a lot of senescent cells that the body cannot get rid of easily so then there will be a build-up of senescent cells and new cells cannot be grown.
what happens after the primary purpose of antagonistic hallmark?
hits hayflick limit its declared senescence so these senescent cells are recognised because they have a specific phenotype and produce SASPs which have inflammatory signals which leads to inflammation.
what happens after inflammatory signals are sent and it causes inflammation in senescent cells
due to ageing to deal with the amount of senescence that has been accumulated or the immune cells or the immune cells are not efficient to remove the senescent cells the body ends up with damaged or senescent cells
what is the relation between senescent cells and cancer?
cancer cells bypass this replication break so the aged and senescent cells continue to replicate and grow and the unlimited growth causes cancer.
Stem cell exhaustion
reason for this is senescence and the repair machinery not working
Haemopoietic cell
blood regenerator cell so it can renew itself and can function in tissue repair and regeneration
why does ageing cause a inability of stem cells
causes inability of stem cells to replenish a tissue or organism so it can’t regenerate itself
what happens when there is a hay flick limit on stem cells?
there is damage accumulated where stem cells can be senescent so they are aged and cannot reproduce
altered intercellular communication
how cell talks to the other cell
3 ways cells communicate
1.peripheral signalling
2.endocrine signalling
3.synaptic signalling
Peripheral signalling
transmitted to adjacent cells which are in close together so once cell releases hormone which the next cell has the receptor for the certain ligand and then change the function
Endocrine signalling
certain hormone is released into blood e.g insulin is released from pancreatic beta cells intro blood and function on other parts of body like liver and recpetors on this receive the hormone and do the function.
Synaptic signalling
neurotransmitters are transported by neuronal axons and target cells bind to receptor and do action potential
how is the communication between cells effected during ageing?
During ageing the communication is not there as messaging is not received and there it too much information being received
Inflammaging
chronic low grade systematic inflammation causes age related disease
what is senescent cell(pro inflammatory signals)
cytokines
3 ways inflammaging can be caused
1.accumalation of proinflammatory tissue damage
2.failure of dysfunctional immune system to effectively clear pathogens
3. senescent cells produce proinflammatory signals
