Cellular ageing

Question 1

Explain DNA damage

Answer 1

Exogenous and endogenous factors damage
Most are repaired by enzyme processes, those that are not accumulate as cells age
Eg ROS (reactive oxygen species)

Question 2

Cellular senescence

Answer 2

Replicative senescene = all normal cells have limited capacity for replication, after a fixed no. of divisions cells become arrested in a terminally non dividing state

Question 3

Cellular senescence mechanisms

Answer 3

telomere shortening = usually at the ends of DNA to prevent fusion and degradation
When somatic cells replicate a small amount of telomere is not replicated
Without the telomere protection the DNA is seen as broken, thus crest occurs
Telomerase controls telomere length
Telomerase is a RNA-protien complex that uses its RNA to add nucleotides to chromosomes ends

Telomerase activity is expressed in germ cells and is present at low levels in stem cells, but it is absent in most somatic tissues. Therefore, as most somatic cells age, their telomeres become shorter and they exit the cell cycle, resulting in an inability to generate new cells to replace damaged ones. Conversely, in immortalized cancer cells, telomerase is usually reactivated and telomere length is
stabilized, allowing the cells to proliferate indefinitely.

Question 4

Defective protein homeostasis

Answer 4

Two things that control it

1. Maintaining proteins correctly folded
2. Autophagy-lysosome system and ubiquitin-proteasome system which degrade misfolded proteins

• both are impaired with ageing

Question 5

Structural and biochemical changes with cellular ageing

Answer 5

Long lived post-mitotic cells
lipfuscin accumulate common
Senescent cells
Cytologically detectable heterochromatin foci
Increased volume
Flattened profile if adherent to a basement membrane or other scaffolding

Biochemically
senescent cells biochemically have different indicators and are still metabolically active