Monday, 18 February 2013

Why do we die?

Owen Gethings

They say that there are two certainties in life, death and taxes. As I am not an economist I do not feel qualified to comment about the state of the taxation system. As a biologist, however, I feel I am more than qualified to explain the notion of death. As a living organism we abide by several rules: we are born, we grow, we make mistakes, we reproduce and inevitably, we die. But why do we die? Organisms grow old, wither and die because we are no longer needed. There is no divine utterance regarding the meaning of life that once spoken will change the course of humanity forever. From a purely biological stand point, we are here to reproduce, and once we do, we die. This is the logic of the selfish-gene theory, coined by Richard Dawkins to explain the purpose of staying healthy, increasing longevity and maximising reproductive potential.

Different organisms go about this in different ways. If you are a salmon, an oyster or a dragonfly then this process is over very quickly. You reproduce, lay your eggs somewhere safe and hope for the best. If you are a dolphin, a whale or an elephant this process is not so simple. You must reproduce, raise your offspring, provide them with food and guide them safely to sexual maturity and inevitably reproduction. As humans, we tend to play a much larger role in our offspring’s life. As grandparents, we often play a large part in the lives of our grandchildren, meaning it is beneficial for us to stay around longer.

Eventually however, our bodies can no longer carry on the way they used to. We begin to age, we ache, we lose our memory, and we lose our hearing and vision. Our once faithful heart that has been pounding away for years begins to deteriorate and fail, and eventually we die. The main reason we die is not known, but it is believed to be a combination of oxidative stress, gene regulation and cellular degradation.

Cellular degradation
Each time a cell divides via mitosis, the DNA is unravelled and information contained within this DNA is copied. At the end of each strand of DNA are the telomeres. The telomeres prevent DNA from spiralling or fusing with other strands. Think of them as book ends on your bookshelf. Each time the DNA is copied, the telomeres are shortened until finally the DNA can no longer be copied and apoptosis (programmed cell death) takes over and kills the cell before it can mutate and cause a problem. This process is known as the hayflick limit, and dictates the amount of times a cell can reproduce before it dies. In humans the hayflick limit is approximately 40-60 times. This process does not occur in cancer cells, due to an enzyme called telomerase, which inhibits the shortening of the telomeres so the cell doesn't die.

Oxidative stress
During cellular respiration, reactive oxygen species (ROS) are formed as a by product of aerobic respiration. The mitochondria produce a large amount of these molecules during oxidative phosphorylation via the electron transport chain. These ROS molecules include superoxide anion, hydroxyl radical and hydrogen peroxide (H2O2). These molecules have the potential to directly damage DNA, protein and lipid reserves and as such, are implicated in the aging process. Metabolic rate has been linked with longevity. Naked mole rats, for example can alter their metabolic rate in response to nutrient availability. When food is scarce, they slow down their metabolism. It is also interesting that unlike other mammalian species, the naked mole rate does not maintain homeostasis in the normal mammalian fashion. The naked mole rate is a thermoconformer as opposed to a thermoregulator, meaning it maintains its body temperature according to ambient temperature. As a result it can live 10 times longer than other rodent species. If we compare a mouse, whose average lifespan is ~4 years, with a Galapagos tortoise, whose average lifespan is ~190 years we begin to notice a pattern emerging. The mouse is a very active species, whose heartbeat is much faster than that of the tortoise, implying that mice have a much greater demand for energy than the tortoise so therefore have a higher rate of metabolism to meet those energy demands.

Gene regulation
The idea that we have genes that control when we die has long been hypothesised and in 1993 gained strength. A study was carried on the nematode Caenorhabditis elegans and its response to oxidative damage. The team found a specific gene; DAF-2, that once mutated increased the longevity and increased resistance to oxidative stress. The worm’s average lifespan is ~2 weeks, however those worms that had mutations in DAF-2 lived twice as long as those worms that did not.

Although we do not know the exact reason why different species age and die at varying rates, we do know that a combination of gene function, oxidative stress and cell degradation are the most probable causes.