Recently, Hilda Clulow passed away at a great age of 111, she was the UK’s oldest person. She was born on 15th March 1908 and witnessed momentous events including the discovery of antibiotics, the moon landing and the release of the first iPhone. It is unlikely that many of us will live to this great age, as the average life expectancy in the UK is only 80 years old, which is 31years less than Mrs Clulow’s record age.
Why even with improvements in medicine, is this? This is one of the unanswered quest ions of modern science. We still do not have a conclusive reason why with the passage of time our bodies age. Scientists have come up with many theories why our bodies biologically age, however, the common theory is that it is a combination of factors and not linked to one single cause.
One theory states that over time as our cells divide mutations accumulate and this accumulation can cause problems for the human body. On average, a human cell will divide between 50-70 times before cell death. There are trillions in our body so it is likely that some cells will not replicate correctly leading to mutations in our cells. Mutations in cells can also be caused by mutagens, for example, ultraviolet radiation. Most of the time, the mutations are harmless and DNA repair mechanisms fix the damage, but errors can slip through as we age. Ageing has been linked to the deterioration of these DNA repair mechanisms. This deterioration allows for permanent errors to become more common as we grow older. If the cell with mutated DNA is not corrected then, they can pose a health risk, for example, tumour cells contain a mutation which affects the cell’s genes which control cell division causing them to divide uncontrollably. This risk increases as we age due to the deterioration of the DNA repair mechanisms.
If a cell’s DNA becomes too damaged it will enter apoptosis where the cell dies at a programmed rate or the cell will become senescent. Senescence is a process where the cells kill themselves or become nonreplicating and become dormant.
However, it has been suggested that an accumulation of these cells can speed up cell ageing by releasing inflammatory cytokines (small proteins that are important in cell signalling). This is thought to contribute to atherosclerosis, a disease in which plaque builds up inside your arteries, and other ageing-related diseases. This theory states that ageing is directly affected by the damage to cells over time during division.
Another theory was developed in the 1950s by Denham Harman. It is known as the free-radical theory of ageing and states that ageing is caused by the accumulation of damage inflicted by reactive oxygen species (ROS). ROS is produced in all aerobic cells and is formed from products of oxygen. It can be beneficial to organisms as cell regulators, but in high doses, they become cytotoxic, often leading to cell death. Our cells’ levels of free radical damage increase with age and this has been linked to an increase of ROS over time. The free radical theory may also be used to explain many of the structural features that develop with ageing including DNA damage and a decline in mitochondrial function.
However, in the 1990s, scientists studying model organisms observed phenomena that contradicted the free radical theory. They showed that the enzymes that block the product ion of ROS didn’t extend the lifespan of mice. They found in worms, stressing the mitochondria at a certain stage of development actually increased life span. So we are still unsure whether this theory serves as an explanation to the main reason why we age or is just another factor of ageing.
A final theory states that ageing is due to an accumulation of our cells which lose the ability to replicate correctly. Our DNA strands become slightly shorter each time a chromosome replicates itself. Telomeres help prevent genes from being lost in this process but this means that as your chromosomes replicate, your telomeres shorten. An enzyme called telomerase helps prevent too much damage to your cells. This includes shortening of your telomeres. Telomerase does this by adding additional telomere sequences to the ends of your chromosomes. However, telomerase is only found in certain cells so most cell types in your body don’t have telomerase. This means that most of your telomeres continue to get shorter over time so the DNA polymerase cannot fully replicate the ends of chromosomes in most cells. If the telomeres shrink too much or are damaged, cells enter senescence. This slows the body’s ability to renew itself. Telomere damage has clear effects on ageing. Mice with short telomeres have diminished life spans and reduced stem-cell and organ function, while mice whose telomerase is enhanced in adulthood age more slowly. In humans, mutated telomerase is associated with disorders involving organ dysfunction and elevated cancer risk.
Yet even with all these theories we still have not got an answer exactly why these factors occur and how they function together. Maybe in the future, we will have conclusive proof of why, over time, our body ages, but will that take a couple of years or a couple of lifetimes to find. I guess we will have to wait and see what momentous events we will witness.