The science of aging: Can we live forever, and should we?
The science of aging: Can we live forever, and should we?
Aging to the everyday human is simply the outcome of the passing of time. Aging takes its toll physically, manifesting itself in gray hairs, wrinkles, and memory hiccups. Eventually, the accumulation of typical wear and tear gives way to more serious disease and pathology, such as cancer, or Alzheimer’s, or heart disease. Then, one day we all exhale a final breath and plunge into the ultimate unknown: death. This description of aging, as vague and un-definitive as it may be, is something so fundamentally known to each and all of us.
However, there is an ideological shift happening that may revolutionize the way we understand and experience age. Emerging research on the biological processes of aging, and developing biomedical technologies targeting age-related disease, signify a distinct approach towards aging. Aging, in fact, is no longer considered a time-dependent process, but rather an accumulation of discrete mechanisms. Aging, instead, could be better qualified as a disease itself.
Enter Aubrey de Grey, a Cambridge PhD with a background in computer science, and self-taught biomedical gerontologist. He has a lengthy beard that flows over his reed-like chest and torso. He speaks quickly, words rushing out of his mouth in a charming British accent. The rapid-fire speech could simply be a character quirk, or it could have evolved from the sense of urgency he feels regarding the war he’s waging against aging. De Grey is the co-founder and Chief Science Officer of SENS Research Foundation, a charity that is dedicated to advancing research and treatment for age-related disease.
De Grey is a memorable character, which is why he spends a lot of time giving talks and rallying people for the anti-aging movement. On an episode of TED Radio Hour by NPR, he predicts that “Basically, the types of things you could die of at the age of a 100 or 200 would be exactly the same as the types of things that you might die of at the age of 20 or 30.”
A caveat: many scientists would be quick to point out that such predictions are speculative and there is a need for definitive evidence before making such grand claims. In fact, in 2005, MIT Technology Review announced the SENS Challenge, offering $20,000 to any molecular biologist who could sufficiently demonstrate that SENS claims regarding the reversal of aging were “unworthy of learned debate”. Until now, no one has claimed the full prize except one notable submission that the judges felt was eloquent enough to earn $10,000.This leaves the rest of us mortals, however, to grapple with evidence that is inconclusive at best, but promising enough to merit consideration of its implications.
After sifting through mounds of research and overly optimistic headlines, I’ve decided to only focus on a few key areas of research that have tangible technology and therapies related to aging and age-related disease.
Do genes hold the key?
The blueprint for life can be found in our DNA. Our DNA is full of codes that we call ‘genes’; genes are what determine what colour your eyes will be, how fast your metabolism is, and whether you’ll develop a certain disease. In the 1990s, Cynthia Kenyon, a biochemistry researcher at the University of San Francisco and recently named one of the top 15 women in science in 2015 by Business Insider, introduced a paradigm-changing idea – that genes could also encode how long we live, and switching on or off certain genes could prolong a healthy life span. Her initial research focused on C. Elegans, tiny worms that are used as model organisms for research because they have very similar genome development cycles to humans. Kenyon found that switching off a specific gene – Daf2 – resulted in her worms living twice as long as regular worms.
Even more exciting, the worms did not simply live longer, but they were healthier for longer too. Imagine you live to 80 and 10 years of that life is spent struggling with frailty and disease. One might be hesitant about living to 90 if it meant spending 20 years of life plagued with age-related diseases and lower quality of life. But Kenyon’s worms lived to the human equivalent of 160 years and only 5 years of that life was spent in ‘old age’. In an article in The Guardian, Kenyon laid bare what some of us would only secretly hope; “You just think, 'Wow. Maybe I could be that long-lived worm.'" Since then, Kenyon has been pioneering research into identifying genes that control the aging process.
The idea is that if we can find a master gene that controls the aging process, then we can develop drugs that interrupt that gene’s pathway, or use genetic engineering techniques to alter it altogether. In 2012, an article in Science was published about a new technique of genetic engineering called CRISPR-Cas9 (more easily referred to as CRISPR). CRISPR swept through research labs worldwide the following years and was heralded in Nature as the biggest technological advancement in biomedical research in over a decade.
CRISPR is a simple, cheap and effective method of editing DNA that uses a segment of RNA – the biochemical equivalent of a carrier pigeon – which guides editing enzymes to a target DNA strip. There, the enzyme can quickly snip out genes and insert new ones. It seems fantastical, to be able to ‘edit’ human genetic sequences. I imagine scientists creating collages of DNA in the lab, cutting and pasting genes like children at a craft table, discarding the unwanted genes altogether. It would be a bioethicist’s nightmare to create protocols that regulate how such technology is used, and on whom.
For example, there was uproar earlier this year when a Chinese research lab published that it had attempted to genetically modify human embryos (check out the original article at Protein & Cell, and the subsequent kerfuffle at Nature). The scientists were investigating the potential of CRISPR to target the gene responsible for β-thalassemia, a hereditary blood disorder. Their results showed that CRISPR did manage to cleave out the β-thalassemia gene, but it also affected other parts of the DNA sequence resulting in unintended mutations. The embryos did not survive, which all the more emphasizes the need for more reliable technology.
As it relates to aging, it is imagined that CRISPR can be used to target age-related genes and switch on or off pathways that would help slow the aging process. This method could be delivered, ideally, via vaccination, but the technology is nowhere near close to achieving this goal and no one is able to say decisively if it ever will. It appears that fundamentally re-engineering the human genome and altering the way we live and (potentially) die remains a part of science fiction – for now.
If the tide of aging cannot be stemmed at the genetic level, then we can look to mechanisms further down the path to interrupt the ageing process and prolong healthy lives. At this moment in history, prosthetic limbs and organ transplants are commonplace – spectacular feats of engineering where we have enhanced, and at times altogether replaced, our biological systems and organs in order to save lives. We continue to push the boundaries of human interface; technology, digital reality, and foreign matter are more ingrained into our social and physical bodies than ever. As the edges of the human organism become blurred, I begin to wonder, at what point can we no longer consider ourselves strictly ‘human’?
A young girl, Hannah Warren, was born in 2011 without a windpipe. She couldn’t speak, eat, or swallow on her own, and her prospects did not look good. In 2013, however, she underwent a ground-breaking procedure that implanted a trachea grown from her own stem cells. Hannah awoke from the procedure and was able to breathe, without machines, for the first time in her life. This procedure gained a lot of media attention; she was a young, sweet-looking girl and it was the first time the procedure had ever been carried out in the U.S.
However, a surgeon named Paolo Macchiarini had already carried out pioneered this treatment five years earlier in Spain. The technique requires building a scaffold which mimics the trachea from artificial nanofibers. The scaffolding is then ‘seeded’ with the patient’s own stem cells harvested from their bone marrow. The stem cells are carefully cultured and allowed to grow around the scaffolding, forming a fully functional body part. The appeal of such an approach is that it drastically reduces the possibility of the body rejecting the transplanted organ. After all, it is built from their own cells!
Additionally, it relieves pressure from the organ donation system which rarely has enough supply of desperately needed organs. Hannah Warren, unfortunately, passed away later the same year, but the legacy of that procedure lives on as scientists battle over the possibilities and limitations of such regenerative medicine – building organs from stem cells.
According to Macchiarini in the Lancetin 2012, “The ultimate potential of this stem-cell based therapy is to avoid human donation and life-long immunosuppression and to be able to replace complex tissues and, sooner or later, whole organs.”
Controversy soon followed this seemingly jubilant period. Critics voiced their opinions in early 2014 in an editorial in the Journal of Thoracic and Cardiovascular Surgery, questioning the plausibility of Macchiarini’s methods and demonstrating concern over high mortality rates of similar procedures. Later that year, the Karolinska Institute in Stockholm, a prestigious medical university where Macchiarini is a visiting professor, launched investigations into his work. While Macchiarini was cleared of misconduct earlier this year, it does demonstrate the hesitation in the scientific community over missteps in such critical and new work. Nevertheless, there is a clinical trial currently underway in the U.S. testing the safety and efficacy of the stem-cell engineered tracheal transplantation and the study is estimated to be completed by the end of this year.
Macchiarini’s novel procedure is not the only step forward in creating bespoke organs – the advent of the 3D printer has society ready to print everything from pencils to bones. One group of researchers from Princeton managed to print a prototype of a functional bionic ear in 2013, which seems like aeons ago given how fast the technology has been developing (see their article in Nano Letters). 3D printing has gone commercial now, and there may well be a race for biotech companies to see who can market the first 3D printed organ.
San Diego-based company Organovo went public in 2012 and has been using 3D printing technology to advance biomedical research, for example, by mass producing tiny livers to be used in drug testing. The advantages of 3D printing is that it doesn’t require the initial scaffolding and it provides much more flexibility – one could potentially interweave electronic infrastructure with the biological tissue and insert new functionalities into organs. There are no signs yet of printing fully fledged organs for human transplantation, but the drive is there as indicated by Organovo’s partnership with the Methuselah Foundation – another brainchild of notorious Aubrey de Grey.
The Methuselah Foundation is a non-profit organization which funds regenerative medicine research and development, reportedly donating over $4 million to various partners. While this isn’t much in terms of scientific R&D – according to Forbes, big pharmaceutical companies can spend anywhere from $15 million to $13 billion per drug, and biotechnology R&D is comparable – it is still a lot of money.
Living longer and the tragedy of Tithonus
In Greek mythology, Tithonus is the lover of Eos, Titan of the dawn. Tithonus is the son of a king and a water nymph, but he is mortal. Eos, desperate to save her lover from eventual death, begs the god Zeus to gift Tithonus immortality. Zeus does indeed bestow immortality upon Tithonus, but in a cruel twist, Eos realizes that she forgot to ask for eternal youth as well. Tithonus lives forever, but he continues to age and lose his faculties.
“Immortal age beside immortal youth / And all I was, in ashes” says Alfred Tennyson in a poem written from the perspective of the eternally damned man. If we are able to persuade our bodies to last twice as long, there is no guarantee that our minds will follow suit. Many people fall prey to Alzheimer’s or other types of dementia before their physical health starts to fail. It used to be widely claimed that neurons cannot be regenerated, so cognitive function would irreversibly decline over time.
However, research has now firmly established that neurons can in fact be regenerated and demonstrate ‘plasticity’, which is the ability to form new pathways and create new connections in the brain. Basically, you can teach an old dog new tricks. But this is hardly enough to prevent memory loss over a lifetime of 160 years (my go-to future lifespan would be laughable to de Grey, who claims humans may reach as old as 600 years old). It is hardly desirable to live a long life without any mental faculties to enjoy it, but strange new developments indicate that there might be hope yet to save our minds and spirits from withering.
In October 2014, a team of researchers at Stanford University began a highly publicized clinical trial that proposed to infuse Alzheimer’s patients with blood from young donors. The premise of the study has a certain ghoulish quality, of which many of us would be skeptical, but it is based upon promising research already done on mice.
In June 2014, an article was published in Nature magazine by a group of scientists from Stanford detailing how transfusing young blood into older mice actually reversed the effects of aging in the brain from the molecular to the cognitive level. The research showed that the older mice, upon receiving young blood, would grow back neurons, show more connectivity in the brain, and have better memory and cognitive function. In an interview with the Guardian, Tony Wyss-Coray – one of the lead scientists working on this research, and a professor of neurology at Stanford – said, “This opens an entirely new field. It tells us that the age of an organism, or an organ like the brain, is not written in stone. It is malleable. You can move it in one direction or the other.”
It is unknown exactly what factors in the blood are causing such dramatic effects, but the results in mice were promising enough to allow for a clinical trial to be approved in humans. If the research proceeds well, then we could potentially identify singular factors that rejuvenate human brain tissue and create a drug that may well reverse Alzheimer’s and keep us solving crosswords until the end of time.