Biology Lecture No. 24: Oxygen & Ageing
Wednesday April 4 , 2012
-Ageing is defined as the progressive impairment of function with an increasing probability of death.
There are many factors that determine lifespan among humans, these include: Environmental factors
(where one lives), genetic factors (if one has certain genes expressed and certain ones not), and
metabolic factors (the state of one’s mitochondria in relation to cellular respiration).
-Apparently, developed countries are home to individuals with longer lifespans due to improved
sanitation (especially with clean water) and advancements in health care, which modern-day humans
rely on for the maintenance of their health.
-There have also been various hypotheses discussed about ageing being linked to oxygen as the terminal
electron acceptor in cellular respiration.
The Paradox Of Aerobic Life:
-It has been documented that many anaerobic organisms die when exposed to oxygen. This is profound
because such organisms that grow by fermentation (relying heavily on glycolysis) are not just displaying
inability to use oxygen, but induced death from oxygen exposure.
-Certain hyperoxia treatments used to be a regular occurrence in hospitals in which patients would
receive the maximum supply of oxygen (100%). Nowadays, pure O is never2used for procedures like
newborn resuscitation. In the event that isochemia occurs, a reperfusion injury whereby tissue was
depleted of oxygen for prolonged periods of time, providing 100% oxygen is detrimental to the patient.
-The paradox of aerobic life is essentially that humans require oxygen to survive, but oxygen at the same
time (in large quantities) can be very toxic as well.
Reactive Oxygen Species (ROS):
-The reduction of oxygen to water requires 4 electrons to reach completion. In this reduction reaction
there are steps that yield partial forms of oxygen, which are deadly, by the administration of one
electron at a time.
-A single electron reduction of oxygen gives the ROS superoxide, which becomes hydrogen peroxide
through the addition of an electron and 2 hydrogen ions, a hydroxyl radical by way of another electron
and H ion, and finally water by adding one more electron and 2 other H ions.+
-These partially-reduced oxygen molecules are dangerous because they are strong oxidizing molecules.
Superoxide especially can potentially pull electrons from DNA and proteins, oxidizing biologically
important molecules. -That is precisely why the enzyme superoxide dismutase (SOD) drives the conversion of superoxide to
hydrogen peroxide, whereby the catalase enzyme quickly converts hydrogen peroxide to water.
-It is because these anaerobes (also known obligate anaerobic bacteria) lack these enzymes that
minimize exposure to the formation of partially reduced oxidizing molecules that they suffer from
exposure to oxygen as a result.
The Mitochondria As A Main Source Of ROS:
-The link between the respiratory electron transport chain and reactive oxygen species is, of course, the
mitochondria. But where exactly along the chain are ROS made? It is not cytochrome oxidase that is the
source of ROS as the enzyme actually holds on to individual electrons until four are totalled. It then
donates all four of these electrons simultaneously to oxygen.
-The major site for ROS is in fact the ubiquinone pool; where electrons are fed through, but that very
easily accumulate. Approximately, for every 1000 electrons, 1 electron will be picked up by oxygen to
form partially-reduced oxygen (superoxide, to be exact) from ubiquinone. This is why SOD1 (human
version of SOD) is in great abundance in this area.
-It is important to note that the paradox of aerobic life is an inevitable consequence of cellular
respiration. That is to say, the formation and production of ROS is an unavoidable circumstance and it
bound to happen.
-There are a multitude of human illnesses that are the result of the condition of the respiratory electron
transport chain. For example, there are forms of Parkinson’s disease that seem to be based on defects of
NADH dehydrogenase. The enzyme is essentially still operational, but mutations to the gene lower the
-Other examples include patients of amyotrophic lateral sclerosis (ALS) which is related to defects in the
Cytochrome Complex Mutation:
-In a study observing the effects of mutation in the cytochrome complex of worms, the mutant worms
(with a working, but less-effective cytochrome complex) would die. Wild types survive extremely well
through increases in oxygen levels, but the mutants cannot deal with such high levels of oxygen; it is
toxic to them.
-There are molecules that can counteract ROS called antioxidants and if you pre-treat the mutants with
antioxidants, than the mutants live as long as the wild type. Thus it can be said that mutations to the
cytochrome complex affects the formation of ROS. The Mitochondrial ROS Theory Of Ageing:
-This theory demonstrates the notion that ageing is linked to disease through the state of mitochondrial
function. Alterations in mitochondrial function (especially with age) lead to elevations in mitochondrial
dysfunction. This eventually leads to further formation of ROS