How long would you like to live for? Is there a limit to how long we can live for? These are not questions you hear often, but do not be surprised if they are repeated more frequently in the future. The reason? Life extension. It is the concept of living well beyond the average lifespan. 
Humans are already living longer due to vaccines and improvements in sanitation.  The World Health Organization reported that the average life expectancy at birth increased from 48 years in 1955 to 65 years in 1995, and is projected to rise to 73 years by 2025.  As medical techniques continue to improve, we are more inclined than ever to pursue life extension.  Indeed, from the Epic of Gilgamesh to China’s First Emperor, prolonging life has been an ever-present thought in society. [4, 5] Both individuals failed to escape death, but the idea of life extension ironically lives on. Even so, is it truly possible and what should upcoming doctors and scientists consider if they are to join the most ambitious of quests?
The “Horcruxes” of reality
In the fictional Harry Potter series, “Horcruxes” were objects where people could hide a fragment of their soul in an attempt to take one step towards immortality.  Of course, humans cannot split their souls and hide them in objects, but there are several proposed means by which life extension may be achieved.  This is a testimony to the progress within the life extension field, but there remains much room for improvement.
Eat less, live more
Caloric restriction (CR) is one proposed method for life extension.  In the CALERIE (Comprehensive Assessment of Long term Effects of Reducing Intake of Energy) trial, 218 non-obese humans were randomised to either a control group or an intervention group. The latter aimed for a 25% reduction from baseline energy intake. At the end of the 2-year study period, the intervention group had significantly greater reductions in circulating levels of TNF-α – an inflammatory marker involved in many age-related diseases.  Dr Alexander Miras, winner of the 2014 Nutrition Society Cuthbertson Medal for his research on bariatric surgery, acknowledges that the study was a “good first step,” but argues that “the evidence in humans is lacking.” “A definitive RCT (randomised controlled trial),” Dr Miras continues, “would be very hard, if not impossible.” He also spots a glaring consequence of CR. “My personal approach is to avoid caloric restriction as this leads to hunger which is an unpleasant feeling. I would rather live a shorter life, but enjoy my food.”
One alternative is modulating telomerase activity – as attempted with the anti-ageing TA-65MD® supplement.  Telomeres protect the ends of chromosomes ; they resemble the aglets on the ends of shoelaces. Just as shoelaces would unravel without the aglet, chromosomes would lose vital DNA sequences in the absence of telomeres.  Our cells divide over time, causing telomeres to shorten. Once the telomere becomes too short, cell division ceases, and short telomeres correlate with cellular ageing.  Telomerase is an enzyme that can oppose telomere shortening  – it was what Hamlet was to King Claudius; what exercise is to obesity; and what junior doctors, in England, will be to Jeremy Hunt.
Reactivating telomerase in telomerase-deficient mice reversed both neurodegeneration and degeneration of other organs.  This proved the concept that boosting telomerase activity could have anti-ageing effects, but there is little proof that this occurs in humans. While the mice were telomerase-deficient, humans normally have some telomerase activity. It is like giving food to someone who has been fasting for hours and to someone who has just eaten a three-course meal – the starved individual would unquestionably benefit more. A 12-month long RCT, involving 117 relatively healthy individuals (age range: 53-87), found that low-dose TA-65 significantly increased telomere length when compared to placebo. High-dose TA-65, however, failed to do so. 
Dancing with the devil
What is more worrying than treatments that may be ineffective? Side effects. Telomerase is a double-edged sword and by reducing telomere attrition, it can promote unlimited cell division and cancer.  Elizabeth Blackburn, co-winner of the 2009 Nobel Prize in Physiology or Medicine for her role in the discovery of telomerase, has doubts about exploiting the enzyme. Speaking to TIME magazine, she said, “Cancers love telomerase, and a number of cancers up-regulate it like crazy. . . . My feeling would be that if I take anything that would push my telomerase up, I’m playing with fire.” 
A cauldron of rewards
CR and boosting telomerase activity are just a small sample of life extending techniques, yet there is the notion that such techniques will be intertwined with risks. However, risks are always weighed against rewards, and Gennady Stolyarov, editor-in-chief of The Rational Argumentator and Chief Executive of the Nevada Transhumanist Party, believes life extension would bring “immense and multifaceted” rewards. “The greatest benefit is the continued existence of the individual who remains alive. Each individual has incalculable moral value and is a universe of ideas, experiences, emotions, and memories. When a person dies, that entire universe is extinguished . . . This is the greatest possible loss, and should be averted if at all possible.” Stolyarov also envisages “major savings to healthcare systems” and that “the achievement of significant life extension would inspire many intelligent people to try to solve other age-old problems.”
Former chairman of the President’s Council on Bioethics, Leon Kass, disagrees with this view and argues that mortality is necessary for “treasuring and appreciating all that life brings.”  Hence, increased longevity could lead to an overall reduction in productivity over one’s lifetime. Perhaps Kass is correct, but the array of potential benefits makes it seem unwise to prematurely dismiss life extension. In fact, a survey, which examined the opinions of 605 Australians on life extension, highlighted further benefits – 23% of participants said they could “spend more time with family” and 4% cited the opportunity to experience future societies. 
Learning from our mistakes
Conversely, life extension may result in people enduring poor health for longer periods. 28% of participants in the Australian survey highlighted this concern.  Current trends in life expectancy reinforce their fears. Professor Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham, explains, “Currently, in most countries in the developed world, life expectancy is increasing at approximately 2 years per decade, but healthspan (the years spent in good health) is only increasing at 1.7 years. This has major consequences . . . as more of later life is spent in poor health.” This is a consequence of treating “killer diseases” – according to Dr Felipe Sierra, director of the Division of Aging Biology at the National Institute on Aging. “The current model in biomedicine,” says Dr Sierra, “is to treat one disease at a time. Let’s imagine you have arthritis; cancer; and are starting to develop Alzheimer’s disease. So what do we do? We treat you for cancer. You now live longer with Alzheimer’s disease and arthritis.” A better approach is clear to Dr Sierra who stresses the importance of compression of morbidity – “the goal is to live longer with less time spent being sick.”
Learning from our successes
Even with Dr Sierra’s approach, individual boredom and social implications, including overpopulation, would still be problems. According to Stolyarov, the boredom argument does not hold up when facing “human creativity and discovery.” He believes humans could never truly be bored as “the number of possible pursuits increases far faster than the ability of any individual to pursue.”
In his novel Death is Wrong, Stolyarov explained that the idea that society could not cope with a rapidly expanding population was historically inaccurate. The current population “is the highest it has ever been, and most people live far longer, healthier, prosperous lives than their ancestors did when the Earth’s population was hundreds of times smaller.”  If it has been achieved in the past, who is to say our own society – one far more advanced than any before it – cannot adapt?
Life extension research is quietly progressing, and there is a good chance that it will eventually come to fruition. Although there are doubts about current techniques, Dr Sierra draws attention to novel interventions, such as rapamycin, which “delay ageing in mice.” He concludes that the next challenge is to “develop measures than can predict whether an intervention works in a short-term assay.” Such measures would provide the scaffolding for future clinical trials that test life extension techniques.
Given what may be gained, it is no surprise that artificially prolonging life is exciting some in the same way the Tree of Knowledge tempted Eve. The impact on society? Impossible to predict. It would undoubtedly be a big risk, but perhaps in this complex and uncertain scenario, we ought to remember the words of the poet Thomas Stearns Eliot: “Only those who will risk going too far can possibly find out how far one can go.” 
Gerrard Jayaratnam is a student of Biomedical Science at Imperial College London.
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