Molecular hallmarks of ageing 1 Flashcards
Ageing
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.
6 diseases associated with ageing
1.arthritis
2.heart disease
3.cancer
4.diabetes
5.COPD
6.asthma.
are an individual’s hearing and vision effected by ageing?
Yes cause hearing loss and reduced vision or blindness
Life expectancy
average length of time organism is expected to live-80 years
Lifespan
max time organism is expected to survive -125 years
Health span
percentage of individuals life where they live in good health
Biological age
age that determine the health of organs and tissues and cells in an individual
3 factors that can effect someones biological age
1.alcohol
2. stress
3. exercise
Chronological age
refers to actual amount of time a person is alive
primary hallmarks
cause the disease -initiate it and are negative
2 examples of primary hallmarks
1.endogenous damage
2.exogenous damage
3 things in endogenous damage
replication errors, spontaneous reactions, reactive oxygen species(ROS)
what is repair machinery in endogenous damage?
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
what is ROS in endogenous damage?
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
example of endogenous source(ROS)
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.
what is the free radical theory?
ageing is caused by accumulation of damage inflicted by ROS
what happens to the epigenetic alteration when ageing?
Epigenetic alteration accelerates ageing process. At a young age there are many repetitive sequences -transposable elements which are methylated
in epigenetic alteration, what should happen to the transposable elements which are highly methylated
should be suppressed -As an individual grows older they lose methylation pattern-black circles become white circles-global hypermethylation
when ageing happens there is global by-methylation, what will this do to the methylation pattern?
loss of methylated pattern and most genes become active
what are the misfolding/structural changes of loss of proteostasis ?
The protein needs to be folded properly in order to function and if not, they cannot function and the whole cell cannot function.
with ageing what happens when there is a change of loss of proteostasis
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
secondary hallmark
response to the damage from the primary can be positive or negative -which can damage cells and organs
integrative hallmark
physiological changes that can be seen in elderly -links to phenotype in ageing
2 things of integrative hallmark
-stem cell exhaustion-no new cell
-altered communication-no coordination
antagonistic hallmarks
response to damage caused by primary hallmarks
3 examples of antagonist hallmark(response to damage from primary hallmark)
-mitochondria dysfunction-no energy
-deregulated nutrient sensing-reducing nutrient uptake to reduce overload to damaged cells
-cellular senescence -frozen in time
Double stand break(DSB)
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
Telomere
repetitive nucleotide sequences at the end of chromosomes
What is the role of a telomere?
protect the end of chromosomes from decay and fusion with other chromosomes
Seqeunce:AGGGTT
how does the cell divided during ageing effect the telomeres
as you age the cell divides, it replicates and there is a loss so telomeres get shorter
how do telomeres lead to genomic instability and malfunction in protein of cells
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.
Telomere theory
ageing is caused as a result of replication dependent shortening of telomere that protect the end of chromosomes -genome instability
Cancer
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.
In methylation what does the white circle represent?
unmethylated
in methylation, what does the black circle represent?
methylated
Unmethylated
promoters allow transcription factors to bind to promoter, the gene is then transcribed meaning its active
Methylated
transcription factor cannot bind to so there is no transcription
Tumour suppressor genes
are methylated meaning they are active so they supress tumours
if tumour suppressor genes are methylated with age what will this cause?
cancer
DNA methyltransferase 1(DNMT1)
enzyme responsible for maintaining DNA methylation pattern as cell divides
what is the role of DNMT1?
maintains the pattern ; the enzyme makes sure to copy it every time
IN DNMT1, with ageing how is the methylation machinery effected?
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.
