Hayflicks, Telomeres, Aging Theories Flashcards
what hayflicks limit ?
they are cells that are grown in vitro tht have a fixed number of times they can divide before they die
what were hayflicks fidings ?
cells from fetal tissue are capable of about 50 population doubling then loosing the ability to divide in vitro and then eventually die
what are Phase I, Phase II and Phase III of hayfliks
Phase 1- 1-3 weeks; period of adjustment for cells
Phase 2 - vigrous growth months
Phase 3 - growth declines and cell alteration where changes are irreversible
what are 4 key aspects of hayflicks findings
- Age of donor
- Species Specific
- Progeria’s
- Cellular Memory
what is the age of donor
it is the doubling of cell correlated to the age of donor where you tend to se ages younger have more ability to population doublle while for older people its lesser
what is species specific ?
population doubling of fetal fibroblasts related to max longetvity of a species , high L.S higher hayflicks limit
what is cellular memory and what happens if you try to freeze them to reset
where the cells have a memory for approx 50 doublings , even when cells are frozen they retain there memory
what is 3 laws from the telomere theory of aging?
- cellular timing
- evidence for a L.s in cultured cells
- linked towards cellular replication
what are telomeres ?
the regions on the end of chromosomes that repeate a. 6 nucleotide sequence ( TTAGGG) and there is a finite number of telemers in somatic cells
what are 4 functions of telomeres
- protect the chromosomes
- seperate chromosomes
- prevent chromosomes fuction
- used in replication so it can attached to the chromsome
why are telomers key for a cells (DNA replication)
During dna replication (chromosome replication ) rna primer is added to where the telomere is and is removed leading the shortening of the chromsomes after each cell divsion and when telemers are shorten till no more cells division stops and cells die
what is a T loop what happens with age
a t loop is formed in young somatic cells by proteins to prevent error of attacking telemers as broken DNA but with age the t loop unravels which can allow for attacking
what 2 things that can shorten (dysfunctional) t-loop telomers leads too
it can lead to cellular aging or apoptosis as it can be seen as DNA damange and p53 is activated that causes it
it can also lead to cancer in absence of p53 as it continuously cell divide and cause genome instability and less gene info to pass on
what is the therotical evidence of telomere aging ?
the telemore length in cultured tissue cells is directly proportional to the age of the cell
how do cell become immortal but why arent they ?
having the enzyme telomeras that can added telomeres back that can exist in fetal germ cells and cancer cells
but they are turned off in somatic cells even though they have the gene
what is the lab evidence for the telomere theory and what does tos prove
using human cells in culture they lengthened the number of telomere on the ends of chromosomes using the enzyme telomerase and extended there hayflicks 50 doubling limit
it proves that re lengthing telomeres reverse aging processes
what happens Mortality Phase 1 (M1) and M2 phase
M1- there is critical telomere loss on chromosomes and signal for irreversble cell cycle arrest (senescent cells )
M2- most cells die due to apoptosis
is the link between telomeres and hayflicks limit ?
yes there is some sort of link as cells with telomere shortening has an approx 50 doubline whilist cells with the telomerase enzyme have has beyond the normal 50 doubling limit
does telomere length extendend life span what proves it
no the telomere length doesnt extend lifespan it only help with aging as mice have longer telomeres than human yet they live 3 years
what are senescent cell and where are they found?
they are growth arrested cell location in the g1 to S transition phase
what are 4 key things about p53
- part of the DDR pathway
- prevents DNA replication at G1/S border
- prevents damaged DNA being duplicated
- if damage is not repaired it will be hel till it dies or undergo apoptosis
what is programmed cell death (apoptosis) and whats the reason for it
natrually programmed death of cells
removing unwanted and damaged cells
what is the 4 steps of apoptosis ?
- chromatic condenses
- distruption of organelles
- cell breaks into small bodies
- cell wrinkles and die
what are the two type of malfunctioning of apoptotic signalling
- insufficient apoptosis
- excessive apoptosis
what 3 things could insufficient apoptosis lead to ?
1.cancer
2. autoimmunity
3. persistent infections
what 3 things could excesive apoptosis lead to ?
- neurodegnerations (alzheimers )
- autoimmunity
- ischaemia(stroke)
what are 3 other theories related to aging ?
- Gene mutation theory
- DNA repair theory
- Cellular Garbage Theory
what is the gene mutation theory and examples
the accumulation of mutations in dna gene that then become irreversible and deleterious leads malfunction of struture and funcitions of protein and leads cell death
sickle cell anemia,cystic fibrous
what 5 things that can cause a mutation ?
- radiation
- free radicals
- toxins and chemicals
- decreased repair system
5.errors during replication
what are 4 supports for the gene mutation
- radiation expose leads to increase in mutation and decrease in LS and cancer
- liver cells from mice that lived (1 year ) had more mutation that mice that lived 3 years
- non smoking young adults have a 6 fold less mutation than 60 year olds
- DNA repair capacity of some cells reduce with age
what is the DNA repair theory ?
as DNA accumulates errors with age there is a decrease in repair mechanism
what can be a cause to the DNA repair theory ?
thymine dimers that results from UV damage and form an abnormality in the back bone
what happens if you try to repair thymine dimers
repairing the dimer leads to an increase risk of Xeroderma Pigmentosum which is a skin caner in young people and leads to death around 25 years
how does the repair of DNA correlate with life span
the ability to be able to repair dna damage can increase life span
what is the cellular garbage theory ?
the accumulation of by products from normal cellular metabolism can found in cytoplasm over time with age
with age what could be found in the cell cytoplasm what reactive what not ?
so lipofusions which are not reactive
reactive:
free radical and other reactive molecules
