Thursday, 30 July 2015

Why We Can't Live Forever

The average life expectancy of the typical human living 100 years ago was 31 years. Since the last century most of us now have a projected life expectancy of just over double that of a person living in the 1900s. The 2010 world average life expectancy at birth is 67.2 years (Provided by the CIA, see reference below), but still we cling to the prospect of extending our lives to live out further into older age. As well as different healthy lifestyle plans, guides to happiness and the abundance of medical care, the turn of the millennium has seen a rise in claims of "Miracle pills" that promise to extend life up to several decades, or even slow the ageing process itself. Pseudoscience or a breakthrough in modern medicine, it is an important field of science that illustrates the often conflicting nature of research. This article aims to outline the reasons why it is so hard for any living thing to biologically lengthen the duration of their lifespan.
3 "causes", or signals, of ageing stand out above the rest. They are as follows:


Telomere Shortening

The chromosomes in our genome carry all of the genes needed for an individual. Humans have 46 arranged into 23 pairs, which are replicated when a cell divides. An enzyme called DNA polymerase (DNA Pol) is needed to replicate the DNA in chromosomes during this process. DNA Pol enzyme has evolved over time to be very efficient at it's job, although one major drawback is that the enzyme falls off, just short of the end of every strand it uses to copy. In effect, the daughter strand produced is shorter than the original piece of DNA which arises concern, as the strand could now be missing important pieces of genetic material not copied across. Luckily organisms have adapted to combat this by protecting their chromosomes with telomeres - long repeats of Thymine and Adenine bases which "coat" the tips of the chromatids. The addition of telomeres at the end of DNA sequences protect coding DNA near the ends, so now where DNA Pol now falls off (in the telomere region) it erases a few codons of essentially otherwise useless fragments of TA repeats.
The human foetus synthesises/lengthens telomeres using Telomerase, an enzyme not normally found in the body after birth. As telomeres aren't replaced or lengthened over time once born, countless cell replication cycles shorten telomere regions over time until they disappear altogether. At that point, any genetic material located at the ends of chromosomes that was before protected would now be directly in the "firing line" of deletion. The absence of telomeres in old age has been linked with dementia as important cognitive genes have been erased during cell replication. Some cells are clever enough to notice when telomeres become a dangerously short length, but destroy their selves in order to prevent gene damage.
The shortening of telomeres cannot be stopped as an individual ages, except with the help of telomerase. Mice genetically modified to possess telomerase have been shown to reverse the signs of their own ageing in several studies. However, the addition of telomerase in somatic/adult human cells causes cancer.


Oxidative Stress

The mitochondria in our cells act like power stations, producing energy for our metabolism, growth and repair. Contrastingly, the process in which these organelles produce energy can actually damage cells in the long term.
Mitochondria are very similar to watermills - they produce a gradient (of protons taken from hydrogen, instead of water current) that is released and channelled through certain structures from one side of a membrane to another. These structures act like rotors, just like the wheel of a watermill, turning to create energy in the form of ATP. At the end of the line mitochondria are left with a handful of electrons that caused the gradient in the first place, so oxygen absorbs these to prevent any reactive species in the environment (reduction). However, often some oxygen atoms are reduced insufficiently causing Reactive Oxygen Species known as Free Radicals. Their reactivity can cause a lot of damage to cell membranes, proteins and even genetic material.
Over time a build up of free radicals has the potential to exert a large quantity of damage to tissue in the body. The build up of free radicals is called Oxidative Stress, and gets larger and more concentrated as an individual ages. Mitochondria can never stop producing energy or the cell will die, which means that free radicals will always be produced. 
There are specific enzymes that regulate these reactive species in the human body, and Vitamins E and C play a role in inhibiting free radicals from reacting with fat and genetic material. However the build-up of oxidative stress over time overtakes the regulatory catalysis of free radicals.

Human Evolution

Organisms live for different amounts of time before they begin to age; oak trees can endure centuries before they start to wither, whereas mice only live for a few years. It was previously thought that the size of an organism positively correlated to it's age but many examples in life have quashed this theory (e.g. smaller breeds of dog nearly always live longer than larger breeds, the same goes with humans too).

Evolution has caused species to live out longer or shorter lives for the reasons of reproduction. The whole point of living, from a biological perspective, is to pass on genes to the next generation by means of producing offspring. After peak maturity/adulthood, reproduction is usually no longer on the cards so ageing begins.
The place of a species in the food chain, it's environment, even it's local population plays a part in determining it's age of sexual maturity, it's age of senescence (ageing) and it's ultimate longevity. To explain how evolution has shaped many species' lifespans, here are a few examples:

- Mice have a lot of selective pressure on their shoulders - they are the perfect food for many predators - so for an individual mouse to have any chance of passing on it's genes it must sexually mature very fast before it's eaten. It takes a mouse no longer than 10 weeks to mature, and once a mate is found the gestation period for a female mouse is only around 19-21 days. After 9 months mice age and die very fast to make way for the new generation of sexually mature young.

- African Elephants are just about at the top of the food chain, by contrast. They live in herds on vast grasslands, often close to water sources. Every year each herd migrates to avoid the dry season, and the female elephant usually gives birth to just one offspring at a time, after a 20 month gestation period.
The life expectancy of an African elephant is 70 years. With no selective pressure from predators, the availability of food, and stable life in a herd, elephants have never needed to adapt to mature quickly. In fact the opposite has probably occurred. The long distance migrations over desolate savannah have caused elephants to adapt to extend their lifespan, increasing that probability of finding another herd for a suitable mate.

In terms of us, humans reside at the very top of the food chain. We are clever enough to shape our own environment which gives us a very comfortable lifestyle. Evolution is easy on us and gives us a long childhood as well as an adulthood of suitable length. Moreover, many males stay fertile even in old age to increase the chances of transferring their genes. Human life expectancy can range from 50-80 years worldwide, but could we be doing anything more to allow evolution to grant us more happy years?





In short, no. Evolution works both ways - we have a set maturation period, set peak reproductive period and a set senescence period. All set by our genes: the ultimate decider of our fate. Genes can endure in two ways: they can live in a single immortal individual or they can be passed on to another. Examples of "immortal" organisms are actually quite abundant in prokaryotic world. Some bacteria can produce spores when in environmentally unfavourable conditions, containing their own DNA. The spores are extremely resilient and can last millions of years. When environmental conditions because favourable the spore develops back into the bacterium. This method of endurance essentially cancels out any need for reproduction.

Unfortunate as some people may think, evolution has virtually decided that we're too delicate for immortality and has chosen to give us the ability to transfer our genes by reproduction. If an individual can reproduce, there comes a time where they have move aside for the next generation. Pretty philosophical.



Figures retrieved from https://www.cia.gov/library/publications/the-world-factbook/rankorder/2102rank.html

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