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Updated: Oct 18, 2015 11:04 IST

The idea of death doesn’t quite make sense to Larry Ellison. “How can a person be there and then just vanish, just not be there?” the flamboyant chief executive of Oracle Inc once famously asked his biographer Mike Wilson.

That was more than a decade ago. Since then, putting his money where his mouth is, Ellison has donated more than $430 million to the exciting albeit emerging discipline of anti-ageing research.

Whether it was Ravan, the demon king, who sought immortality in the Ramayan; or the asurs and devtas churning the ocean during the amrit manthan to produce the elixir of life; or even the ancient Egyptians who articulated the desire to live till the age of 120 years, more than 6,000 years ago, our mythology, history and culture are full of examples of the quest to live forever. Today, thanks to cutting-edge research mostly in the West, going from ‘How long have I got?’ to ‘How long do you fancy you want to live?’ might not be the stuff of utopia or sci-fi any longer.

A new frontier

“150 is the new 50,” announces longevity specialist and neurobiologist Dr Dena Dubal of the University of California, San Francisco. Better healthcare, nutrition, vaccines, technology and other factors which enhance the quality of life, mean people are living longer than ever before in every part of the world.

Since Independence, life expectancy in India has shown a remarkable rise as well. An Indian born in 2015 has a projected average lifespan of 70 years, which is 40 years longer than those born in 1947. We are at par with many South-East Asian countries and marginally better than Pakistan and Bangladesh.

Over the last century, significant innovations in healthcare have contributed towards enhancing life expectancy. If the invention of vaccines to cure small pox, polio, diphtheria and other life-threatening diseases gave it a booster shot in the 1950s, improved diagnostic techniques, surgeries and medical advances are leading the fight against fatalities in 2015.

(Photo: Shutterstock)

Once the efforts of longevity scientists such as Dubal begin to fall into place, the average global lifespan may reach an astounding 150 years!

Of mice and men

Dr AB Dey, professor and head of the department of Geriatric Medicine at the All India Institute of Medical Sciences (AIIMS), Delhi, says most of the exciting futuristic approaches in the realm of longevity research haven’t managed to reach the clinical stage yet.

“The closest they’ve reached is from the molecular stage to the animal-testing stage. The difference between the cellular function of mice and human beings isn’t much. But it so happens, the entire life of mice is 30 months and we are seeking a life-span of 120 years [for humans]. It is difficult to directly extrapolate the research done on mice on humans, but they do provide a strong theoretical support to what we are attempting,” says Dr Dey.

It hasn’t deterred those trying to break the longevity code. Ask the bunch of intrepid scientists at the Dubal Lab in the University of California, San Francisco. For the last five years, using human genetics, neuropsychological testing, genetic mouse models and cell-culture methods, they are investigating how an anti-ageing approach holds promise in developing treatments to improve brain health in ageing and disease.

The most remarkable of these is the manipulation of the Klotho gene. Named after the Greek goddess of fate who spins the web of life, one in five people around the world is known to carry the gene, associated with a longer lifespan and improved heart and kidney function.

“When we tinkered with the molecule and raised Klotho levels in the mice, they lived dramatically longer [30 per cent more than those whose genes had not been manipulated]. The genetically engineered animals also did much better than regular mice at learning how to navigate mazes,” says Dr Dubal.

During a subsequent stage of the research, which involved humans, Dubal’s lab studied 700 people from across the United States. “If they carried a variant of the gene, which gave them higher levels of Klotho, they also displayed better brain function,” adds Dr Dubal.

The colour of money

In 2014, Silicon Valley hedge-fund manager Dr Joon Yun announced the launch of the Palo Alto Longevity Prize that will award one million dollars to a team of scientists which manages to “hack death”. Yun is of the view that it is possible to “solve ageing”. To begin with, the prize will be awarded to those scientists who can restore vitality and extend the life-span of mice by 50 per cent.

Yun’s quest for discovering a longevity breakthrough is just another example of the enthusiasm to disrupt death that is gripping business honchos eyeing the lucrative longevity market.

In 2013, for instance, Google founded a biotech company called Calico with a singular goal: Cure ageing and expand the human life span by as much as 100 years. “[Ageing and illness] affect us all – from the decreased mobility and mental agility that comes with age, to life-threatening diseases that exact a terrible physical and emotional toll on individuals and families,” Google co-founder Larry Page announced at the launch.

Many of these initiatives are believed to have been carried out by Google’s highly secretive research arm known as Google X. Their projects are popular in geeky circles as “moon shots,” owing to the massive undertaking and the ambition involved.

Google isn’t alone. PayPal founder Peter Thiel has also granted $3.5 million to the anti-ageing NGO Methuselah Foundation, which is researching drugs that cure types of age-related damage such as loss of cells and excessive cell division.

Stretching it!

How does your body know it is ageing? There isn’t exactly a clock measuring the moment your cells begin to age. But there are other parameters that can function like cellular clocks.

Located at the tail-end of chromosomes, the shortening of telomeres (the little cuffs that cap chromosomes and erode your lifespan) is believed to be one of the biggest indicators of ageing, say longevity experts.

In simple terms, each time a cell divides itself, the cell copies the chromosome’s DNA and the telomeres get shorter. When they get too short, the cell can no longer divide. So it becomes inactive or “senescent” or it dies. This shortening is associated with ageing, cancer, and a higher risk of death.

Therefore, through the use of mice models, a few good longevity researchers are examining whether the wearing down of the telomere fuse can slow down ageing. “Telomeres shorten with every cell division until they reach a critical length that leads to cell death,” explains Dr Navtej Toor, assistant professor in the University of California, San Diego’s department of Chemistry and Biochemistry. “By lengthening the telomeres, we are attempting to cap the end of chromosomes.”

Scientists are exploring procedures which can manipulate genes and pull out ageing cells. (Photo: Shutterstock)

In 2015, Dr Navtej Toor’s team of researchers threw its hat into the ring to compete for the Palo Alto Longevity Prize with the goal of doubling the life-span of a mammalian model system. “We will be using mice in our research. In my opinion, we can learn a great deal from the mouse model system that could be directly translated into human treatment,” he adds.

Reality check

In labs around the world, longevity researchers are exploring approaches to fight ageing, including testing a variety of agents that can treat life-threatening human conditions.

The drug rapamycin, for instance, given to transplant patients to prevent organ rejection after surgery, has displayed good results in genetic mice models. Usually used to assist organ transplants and treat rare cancers, it has been shown to extend the life of mice by 25 per cent – the greatest achieved so far with a drug – and protect them against diseases of ageing including neuro-degeneration.

Others are trying to manipulate genes and pull out ageing cells. But Dr AB Dey of AIIMS, New Delhi, says at present, none of the futuristic technologies needed to handle age-related diseases is available in India.

A lot of longevity research involves finding the trigger for ageing and then trying to kill that trigger. “In the last 30 years, we have found a good solution to heart attacks. If the person reaches the hospital within half an hour or one hour of the attack, the artery can be opened up and the person can survive. Thanks to such interventions, people are living longer,” says Dey. “What we now need are drugs and interventions to thwart major killers such as stroke, Alzheimer’s and cancer.”

While one sees advancements in animal models, their application for humans at the clinical level is not in sight, at least in India. “In India, most of these disciplines are at a primitive stage of research. Indian institutes haven’t made any path-breaking innovation, yet,” says Dr Dey.

In an essay in the journal Technology Review in 2005, leading biogerontologist Aubrey de Grey, the co-author of Ending Ageing, wrote: “Living forever or postponing death is possible in our lifetimes.” De Grey, the chief scientific officer of the SENS Research Foundation, based in Mountain View, California, works on the development of what he calls “Strategies for Engineered Negligible Senescence” (SENS), to stop ageing.

“In the essay, De Grey said that the futuristic technology required to achieve immortality could include stem cell transplant, programmed cell death (apoptosis), elimination of the telomerase gene, immunotherapy and drugs to break protein cross-linking. All these are now available in theory and in animal labs. However, their clinical application has been a nonstarter,” says Dr Dey.

“But in the next two decades, further refinement of some of these technologies is likely to make a substantial impact in developing countries too,” he adds. “I believe these technologies will be available in India with very, very little delay following their emergence in the West,” says Dr Aubrey de Grey.

In a lighter vein, Dr Dey of AIIMS says we may see these technologies in India sooner than we expect. “Whatever troubles the white man, he’ll find a solution for it. HIV/Aids was controlled because people in the West never wanted control over their sex lives. And at this point of time, ageing is an issue in the West.”

Perhaps, there can’t be anybody better than James Bond to express the desire for longevity. As he puts it in the movie: “So, you live to die another day.”

**

Longevity at what cost

In the movie Highlander (1986) Connor MacLeod is a member of the immortals, a mysterious race who die only when their heads are lopped off. The immortals must battle each other until only one is left to claim the prize: The gift of mortality and the ability to die normally like everyone else.

Average life expectancy has been increasing at an alarming pace around the world. People are living longer, but old age often brings a decline in mental faculties and many researchers are looking for ways to slow or halt such decline.

For a population that is growing rapidly, seven billion people worldwide and counting, cognitive decline could emerge as one of the biggest biomedical challenges, says longevity specialist Dr Dena Dubal of the University of California, San Francisco. “Because of advances in medicine we are living longer,” even if our genetics would otherwise condemn us to an earlier death, says Dubal. “But as we live longer, we come into contact with more illnesses that are brain-related.” Or, medicine to help the brain age gracefully hasn’t really kept pace with medicine that helps the body live longer.

The study of the Klotho gene could one day lead to treatments that help people suffering from dementia, adds Dubal. “If one can boost brain structure and function, maybe that could counter the effects of devastating diseases like Alzheimer’s and Parkinson’s,” she says.

Laura C Carstensen, director of the Stanford Center on Longevity, says longer life is a remarkable achievement but now we need to apply what we are learning to accommodate longer lives. “We need to find cures for Alzheimer’s disease and arthritis, develop technologies that render many age-related frailties invisible…and begin seriously rethinking cultural norms, such as the timing of education and retirement,” she wrote in an article on “Issues in Science and Technology” in 2007.

Another crucial issue before countries such as India and China is building a society that can accommodate people who are living longer.

“The second thing we need for people who live longer is better healthcare,” says New York-based gerontologist Ursula Staudinger, director, Robert N Butler Columbia Aging Center, Columbia University. “We’ve been so inventive to create a culture that supports our bodies for much longer than evolution had ever thought it would support. We need to be ingenious again to develop a health system that supports each and every one in a given society to stay healthy as long as possible,” adds Dr Staudinger.

**

The idea of immortality has inspired a slew of interesting characters, plots and tropes in pop culture, TV and cinema. Here are a few of our favourite immortals of all time:

* The Oscar Wilde character Dorian Gray remains young and handsome while his portrait ages. Gray slowly gravitates toward crime, but his age shows in the face of the painting, which turns monstrous and ugly.

* Created by science fiction author Robert Heinlen, the character Lazarus Long capitalises on a selective breeding programme and blood rejuvenation treatments to live for more than 2,000 years.

* In the TV series Doctor Who, the elixir of life is used by the Sisterhood of Karn in many episodes, including The Brain of Morbius.

* In the Harry Potter universe, witches or wizards can become immortal by drinking the elixir of life, made with the Philosopher’s Stone. (below, left)

*In JRR Tolkien’s Lord of the Rings, Arwen, (above, right) a half-elf maiden, gives up on eternal life to tie the knot with her mortal beloved, Aragorn. She dies soon after him, at the age of 2,901.

* At times, immortality is used as a punishment, or a curse to teach a lesson. Take the example of Ashvaththama from the Mahabharat. As a punishment for killing the five sleeping sons of the Pandavas, he was cursed by Krishna that he would roam the earth without finding any love or hospitality until the end of Kalyug.

* Even mythological characters get tired of living forever. When the Greek goddess Eos asked Zeus to grant her mortal lover, Tithonus, eternal life, she forgot to ask for eternal youth as well. Tithonus lives forever, but grows old and frail and begs for death.

* Similarly, in Douglas Adams’s The Hitchhiker’s Guide to the Galaxy, the alien Wowbagger accidentally turns himself into an immortal. Bored by eternal life, he decides to insult every living being in the universe, in alphabetical order, to kill time.

*In the X-Men series, the character of Wolverine (below, left) has self-healing powers, which keep him alive and safe from danger. But towards the end of 2014, Marvel started developing a storyline called Death of Wolverine, enabling his enemies to kill him.

*In the TV seriesForever, Dr Henry Morgan (above, right) has been alive for more than 200 years since he worked as a doctor in the African slave trade and was shot when he refused to allow the ship’s captain to kill a slave who may have been suffering from cholera. Since his first death, Henry has never aged, and possesses a unique form of immortality: whenever he is killed, his body vanishes and he reappears a few hours later without clothes in a nearby body of water, unscathed from whatever killed him.

*In Pran’s comic book series Chacha Chaudhary, the character Raaka drinks a herbal potion made by the druid Chakram Acharya and attains immortality.

* In the Manga comic Blade of the Immortal, a samurai is cursed with immortality. Only after slaying 1,000 evil men will the curse be broken – so he can finally die.

* In the sci-fi drama Lost, the mysterious, all-powerful Jacob is responsible for all the unexplained mishaps on the island. He’s said to have lived for more than 2,000 years and caused the plane crash in the first episode. While he mostly remains unseen through the series, viewers get to see him for the first time in season five.

*In the vampire thriller True Blood, ancient vampires abound. Eric Northman (played by Alexander Skarsgård) has lived for thousands of years and even mentions meeting Jesus in his lifetime.

* In the third season of Supernatural, in the episode called Time is On My Side, Dean and Sam Winchester face Dr Benton, who discovered the secret to eternal life in 1816. At the end of the episode, the Winchesters tie him up and bury him in a grave so that he will be forced to endure an eternity buried alive.

* In the Marvel Comics universe, the character Nick Fury drinks the Infinity Formula – a form of the elixir of immortality in a bid to gain eternal youth.

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From HT Brunch, October 18

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