Theories of Cell & Systemic Ageing

Question 1

What is an overview of all cell ageing theories?

Answer 1

Theories of cell ageing predict that altered cell function is caused
by intrinsic mechanisms that regulate cell ageing processes

Question 2

What is replicative senescence

Answer 2

The gradual decline and eventual loss of cell division is widely
viewed as a major characteristic of ageing

Question 3

What was Alexis Carrels theory and experiment regarding ageing?

Answer 3

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.

Question 4

What was leonard flicks and paul moorheads theory of ageing?

Answer 4

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:

Question 5

What is the hayflick limit?

Answer 5

the finite number of cell doublings

Question 6

why was hayflicks experiment critercised?

Answer 6

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

Question 7

what are the three phases of senescence?

Answer 7

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

Question 8

What is the criteria for the end of replicative life span

Answer 8

Failure to double in 4 weeks

Question 9

what common features are present in senescent cells

Answer 9

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)

Question 10

What are HeLa cells?

Answer 10

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

Question 11

What are the two theories about the mechanism of replicative senescence?

Answer 11

Damage error theories

programmed theories

Question 12

What is damage/error theory?

Answer 12

replicative senescence and cell

ageing are caused by random (stochastic) errors / events

Question 13

What is programmed theory?

Answer 13

Replicative senescence and cell ageing

are explained genetic and programmed cell-death mechanisms

Question 14

What is one cause of cellular ageing

Answer 14

Intracellular accumulation of damaged proteins

Question 15

What is molecular fidelity?

Answer 15

Maintaining proper structures of molecules

Question 16

What factors effecting molecular fidelity?

Answer 16

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

Question 17

What is oxidative stress theory?

Answer 17

predicts that the
intracellular accumulation of damaged bio-molecules results
from reactions involving oxygen containing free radicals

Question 18

What is telomere shortening theory?

Answer 18

predicts that repetitive
replication of chromosomes shortens the telomere to a point
where no further replication can occur

Question 19

What is mitotic clock theory?

Answer 19

predicts that cell senescence
occurs when old mitotic cells sense short telomeres, which, in
turn, cause cell cycle arrest between G1
– S phase transition

Question 20

how can senescent cells leave the cell cycle?

Answer 20

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

Question 21

What benefits and mechanisms of apoptosis?

Answer 21

• 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)

Question 22

What are damages and mechanisms of Necrosis?

Answer 22

• 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

Question 23

What are 3 programmed theories?

Answer 23

1) programmed longevity theory (genes switched on / off)
2) endocrine theory (hormones control / pace ageing)
3) immunological theory (peaks at puberty then declines)

Question 24

What does programmed theory imply?

Answer 24

that there is an ageing timetable

regulated by gene expression or biological clocks

Question 25

What does damaged/error theory imply?

Answer 25

That errors / damage caused

randomly or by external factors accumulate in cells / tissues

Question 26

What are the damaged/error theories?

Answer 26

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)

Question 27

Recommend more reading on intrinsic mechanisms

Answer 27

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