Theories of Cell & Systemic Ageing Flashcards
What is an overview of all cell ageing theories?
Theories of cell ageing predict that altered cell function is caused
by intrinsic mechanisms that regulate cell ageing processes
What is replicative senescence
The gradual decline and eventual loss of cell division is widely
viewed as a major characteristic of ageing
What was Alexis Carrels theory and experiment regarding ageing?
used chicken heart cells and kept replacing broth to support cell growth and replication, cultures where maintained for 36 years and led to conclusion cells where immortal. however was eventually discoved broth contained new cells, so cultured cells where new and not immortal.
What was leonard flicks and paul moorheads theory of ageing?
studied biochemical
mechanisms that transformed ‘normal’ cells into cancer cells:
~ they worked on embryonic fibroblasts assuming they would
be affected less by environmental / lifetime influences
• The embryonic cells were separated from each other using the
connective tissue digesting enzyme ‘trypsin’ and then placed in
a growth medium in cell culture flasks:
~ the growth medium contained physiological levels of salts
and essential nutrients as well as cell-free animal serum
• After months of sub-culturing Hayflick & Moorhead discovered
that cells stopped dividing after 40-60 population doublings:
What is the hayflick limit?
the finite number of cell doublings
why was hayflicks experiment critercised?
cell cultures might have developed chromosomal damage
causing cells to die after 40 – 60 population doublings:
~ it was also suggested that there could be sex differences
what are the three phases of senescence?
Phase I: slow grow for the first 10-12 population doublings in
growth medium – may last 2-3 months
Phase II: more rapid and constant proliferation rate for the next
30-40 population doublings – may last 8-9 months
probably due mutations that transform the cells
Phase III: declining cell proliferation and loss of viable cultures
after 40 – 60 doublings – may take 12 months
What is the criteria for the end of replicative life span
Failure to double in 4 weeks
what common features are present in senescent cells
Arrest in cell devision eg. lengthened cell cycle cell function alterations eg. decreased RNA synthesis immunity associated function (increased inflammatory cytokines) morphological alterations (enlarged cells)
What are HeLa cells?
cells that grow well in cell culture, cultured from a malignant cervical umour in 1951
limited in studying a whole organism but useful in biochemical mechanisms
What are the two theories about the mechanism of replicative senescence?
Damage error theories
programmed theories
What is damage/error theory?
replicative senescence and cell
ageing are caused by random (stochastic) errors / events
What is programmed theory?
Replicative senescence and cell ageing
are explained genetic and programmed cell-death mechanisms
What is one cause of cellular ageing
Intracellular accumulation of damaged proteins
What is molecular fidelity?
Maintaining proper structures of molecules
What factors effecting molecular fidelity?
a single amino acid error in a protein can reduce
its function or lead to cellular elimination
3
Evolution / natural selection have selected several genes that
maintain ‘molecular fidelity’ during development
Mechanisms that repair / replace damaged molecules are help
maintain molecular fidelity, and reducte age-related decline
What is oxidative stress theory?
predicts that the
intracellular accumulation of damaged bio-molecules results
from reactions involving oxygen containing free radicals
What is telomere shortening theory?
predicts that repetitive
replication of chromosomes shortens the telomere to a point
where no further replication can occur
What is mitotic clock theory?
predicts that cell senescence
occurs when old mitotic cells sense short telomeres, which, in
turn, cause cell cycle arrest between G1
– S phase transition
how can senescent cells leave the cell cycle?
Some undergo apoptosis: ~ programmed cell death ~ apoptotic cells are cleared by macrophages • Some undergo necrosis: ~ cells undergo lysis which promotes inflammation • Some immune cells become anergic: ~ non-responsive to antigen
What benefits and mechanisms of apoptosis?
• Beneficial series of genetically programmed biochemical events that lead to cell death • Establishes a healthy balance between rates of cell division (mitosis) and cell death • Helps prevents tumors • Involves nuclear fragmentation, chromatin condensation, DNA fragmentation), apoptopic body formation, membrane blebbing and cell shrinkage • Apoptotic cells / bodies engulfed by macrophages (phagocytes)
What are damages and mechanisms of Necrosis?
• Detrimental process of damage caused by products of metabolism (free radicals) or external factors such as infection, toxins, or trauma • Necrosis causes premature death of cells and living tissue • Involves respiratory poisons and hypoxia causing ATP depletion, metabolic collapse, cell swelling, membrane disruption, cell rupture and inflammation (often chronic) • Debris may not be engulfed
What are 3 programmed theories?
1) programmed longevity theory (genes switched on / off)
2) endocrine theory (hormones control / pace ageing)
3) immunological theory (peaks at puberty then declines)
What does programmed theory imply?
that there is an ageing timetable
regulated by gene expression or biological clocks
What does damaged/error theory imply?
That errors / damage caused
randomly or by external factors accumulate in cells / tissues
What are the damaged/error theories?
1) wear and tear theory (cells / tissue wear out)
2) rate of living theory (high metabolic rate = short life span)
3) cross-linking theory (accumulation of protein cross links)
4) free radical theory (superoxide & free radical damage)
5) somatic DNA damage theory (unrepaired genetic damage)
Recommend more reading on intrinsic mechanisms
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