How to Live Forever - The Science of Immortality

How to Live Forever - The Science of Immortality
The Apotheosis of Hercules - François Lemoyne 

Death. It is a sensitive topic to some, a source of fear for many, yet patiently waits for all of us at the end of our respective journeys. As mortal beings we have learnt to accept this fact while we continue about our short, pathetic, and fleeting lives, before passing on and eventually being forgotten within the span of decades – what is but a microsecond compared to the life spans of beings such as stars, or even the universe itself.

As a result, the dream of immortality is one that is shared universally by different cultures and religions alike, throughout the brief history of humans. Perhaps most notably in Chinese history, rulers and kings were infamous for being obsessed in the pursuit of eternal life through obtaining the “pill of immortality”, a fabled medicine said to grant the user everlasting vitality and even bring the dead back to life. Although the experiments failed, it resulted in the accidental invention of gunpowder, and even tofu (according to some legends). Ironically, many emperors such as Qin Shi Huang died a premature death as the pills often contained high concentrations of heavy metals such as mercury or lead. Today, most people seem to have abandoned what they believe is a naïve and hopeless fantasy, without realising that nature’s “pill of immortality” exists discreetly among us, hidden tantalizingly out of sight.

Traditional Chinese painting depicting a man practicing alchemy in search of the pill of immortality 

In the murky, cold depths of the Arctic waters off the coast of Greenland, a lone shark blindly meanders. Its eyes have been rendered to a near blind state by worm-like parasites, and its skin is cracked and wrinkled with age. Indeed, the Greenland shark possesses the greatest lifespan among its fellow vertebrates, averaging at around 400 years, although some Greenland sharks have been recorded to be over 500 years old. Their astounding vitality is largely attributed to their extremely slow rate of metabolism. In fact, the Greenland shark seems to lead a rather slow life in general – its swim speed is one of the lowest across all fish species at 1.22 km/hour, paradoxically slower than the prey it consumes. Even before the Greenland shark is born, it has to spend a gestation period of 8 – 18 years before being let out of its mother’s womb.

The Greenland shark, photographed by Nick Caloyianis

The Greenland shark, along with animals such as lobsters or plants such as aspen trees, are all examples of organisms which display negligible senescence – meaning that their health does not deteriorate as their chronological age increases. As long as they have enough food and avoid predators, they can theoretically live forever. In humans, the body weakens with age, and becomes more susceptible to disease and injury. As surgeon and author Atul Gawande puts it in his book Being Mortal, “Old age is not a diagnosis. There is always some final proximate cause that gets written down on the death certificate – respiratory failure, cardiac arrest”. To be clear, there is a stark difference between senescence and aging – senescence is aging in the biological sense, the gradual deterioration of the bodily functions, whilst aging is but the increase of the time spent alive for an organism, without the implications attached. This is important to consider when dealing with non-senescent organisms which age, like all living organisms, but do not senesce.

Why most living organisms experience death is a topic under heavy debate even now among biologists, with many theories being developed about it. One of the most iconic theories is developed by Sir Peter Medawar, a Nobel prize laureate most known for his work on organ transplantation. His theory of senescence published in 1952 used the idea of genes being the base unit for natural selection as a foundation for his reasoning – the goal of all sexually reproducing organisms is to act as carriers to spread their genes – such that the life of the organism is only a second priority to the survival of its genes. Once an organism has reared offspring with the same genes as itself, its life or death matters not. To summarise his words, he theorises that the age of death is greatly related to an organism’s “reproductive value”. Since organisms tend to reproduce as soon as they reach sexual maturity, any potentially lethal genes (such as one that would cause cancer) that act later during the organism’s stage of life would have much less of an effect on the organism’s ability to reproduce and bear children, allowing the spread of their lethal phenotypes within the species without significant consequence. Therefore, older organisms have a lesser “reproductive value” because they would have already had many offspring and spread their genes, and any genetic disease which were to infect them would have no repercussions in the long run.

Indeed, the secret to immortality lies within the genetic composition of the organism. The one thing which all non-senescent organisms have in common is the ability to indefinitely replenish and repair their DNA and thus cells. This is because one of the main theorised reasons for how we age is through accumulative damage to the DNA (note that this is different from mutations, in that it affects the chemical structure of the DNA, not the base pairing sequence). To explain in greater detail, all cells except for embryonic stem cells are unable to undergo cell division indefinitely. Eventually, they reach what is known as the Hayflick limit and enter a state of apoptosis, a programmed cell death where the immune system will kill off the cell. The Hayflick limit itself is defined by the length of telomeres in each chromosome the cell contains: Telomeres, which are essentially repetitive non-coding sequences of DNA, can be found at both ends of a chromosome, where the genes can be found in between. Due to the nature of cell division, every time a cell divides a portion of their chromosomes are damaged. Therein lies the main function of telomeres – they do not code for any proteins, but rather act as a form of protection against the damage caused to the chromosome. Unfortunately, the entire length of telomere will eventually run out after enough cell divisions, reaching the Hayflick limit and causing the actual genetic coding material of the chromosome to be damaged.

A diagram demonstrating the degradation of telomeres in chromosomes

This field of genetics is still a very relevant and popular field of research today. Particularly in the context of health and medicine, this research is crucial for understanding and solving issues such as cancer. Cancerous cells produce telomerase, an enzyme which stimulates the production and repair of telomeres. This essentially removes the Hayflick limit, allowing them to reproduce indefinitely and out of control into a large tumor. One of the proposed treatments of cancer involves the inhibition of the telomerase enzyme, effectively halting the development of the tumor and preventing its spread throughout the body. On the contrary, stimulating specifically the stem cells in the human body to produce telomerase can also benefit our health greatly. Known as telomerase therapy, synthetic mRNA with the coding sequence for telomerase is injected into stem cells, causing the telomerase enzyme to be produced through protein synthesis. This method of replenishment is shown to reverse the effects of telomere shortening in stem cells by 10 years in a single treatment, whilst having a low risk of mutations leading to cancer as the telomerase is only being produced for a brief amount of time per dose of mRNA.

So could telomerase therapy be the key to eternal youth? It is impossible to tell as of now. What we can be sure of, however, is that the development and research into this field will continue until a conclusion can be made. As of today, scientists have already successfully manipulated the lifespans of animals such as the C. Elegans roundworm, doubling its lifespan and causing it to age slower just by the alteration of a single gene. Although the clinical trials for humans have yet to begin, the prospects are promising and they are likely to have high success rates. Soon, it may be that death will no longer be a threat, but rather, it will be us humans that are waiting patiently to die.