Biology of normal ageing Flashcards
What is normal ageing?
A persistent decline in age-specific fitness components of an organism due to internal physiological degeneration.
Identify processes associated with ageing.
Inflammation
Telomere attrition (weakening)
Epigenetic alterations
Loss of protein homeostasis (proteostasis)
Stem cell exhaustion
Deregulated nutrient sensing
Mitochondrial dysfunction
Altered intracellular communication
Cellular senescence
Define cellular senescence.
Cellular senescence is a process that limits the proliferation (growth) of normal human cells.
What does the ‘Hayflick limit’ propose?
Concept stating that a normal human cell can only replicate and divide 40-60x before it cannot divide anymore, and will break down by apoptosis.
What are telomeres and what is their role in ageing?
Telomeres: repeats of the nucleotide base sequence TTAGG at the end of each chromosome, which protect genome from nucleolytic degradation, unnecessary recombination, repair and interchromosomal fusion.
The biological clock is caused by the progressive shortening of telomeres upon each cell division. Telomere length declines as we age.
What is the process of oxidative stress?
a. Normal metabolism uses oxygen
b. Generates free radicals such as reactive oxygen species (ROS)
–> Free radicals: any molecule with an unpaired electron in an atomic orbital, making them unstable and highly reactive (ex. superoxide)
* Formed due to cell’s exposure to UV light, air pollution, ionising radiation, smoking, metabolism, inflammation
* Benefits –> can kill invading microorganisms
c. Damages DNA, proteins, lipids, membranes
d. Damaged lipids + proteins accumulate in cells like neurons & cardiac myocytes
What is mitochondrial ageing?
a. Mitochondria is very susceptible to damage
b. During normal respiration, a small number of e- leak from the mitochondria and form ROS. As the cell ages, e- leakage increases –> more ROS generated.
What are antioxidants?
Antioxidants: a molecule stable enough to donate an e- to a free radical and neutralise it, thus reducing its capacity to damage.
a. Superoxide dismutase (SOD) is an enzyme that catalyses ROS to hydrogen peroxide
b. Catalase + glutathione peroxidase (GPx) enzyme catalyse hydrogen peroxide to water and oxygen.
What are some supporting factors for free radical theory?
a. Inserting extra copies of SOD gene extends fruit fly lifespan by 30%
b. Higher levels of SOD + catalase found in long lived nematodes
c. C.elegans treated with SOD lived 44x longer.
d. Mutant worms with mitochondrial defect was restored by SOD + catalase.
How does DNA damage and repair work?
DNA repair functions to stop the cell cycle so that the corrupted genetic information is not propagated. If repair is successful –> resume cell cycle, repair is unsuccessful –> apoptosis
* Species with better DNA repair (higher DNA repair activity) have longer lifespans
