06 January 2023
Is there a cure for aging? The idea may sound like science fiction but there is growing evidence that various kinds of treatment may slow or even reverse the damaging effects of old age.
Serious money is now flowing into the field, with a growing number of clinical trials investigating different anti-aging therapies. The implications are profound. Since aging plays a role in so many chronic diseases, novel therapies that address the physiology of the aging process might one day prevent the onset or mitigate the severity of everything from cancer to dementia.
Indeed, believers in the “geroscience hypothesis” argue that rather than trying to cure Alzheimer’s, heart disease, cataracts or other diseases of aging one by one, it makes far more sense to move up a level by tackling the biology of aging itself.
Few people understand the processes involved better than Professor Dame Linda Partridge of University College London’s Institute of Healthy Ageing, who is also the founding director of the Max Planck Institute for Biology of Ageing in Cologne.
“Previously people thought we just wear out like cars or washing machines, so there is nothing that can be done about it and there’s nothing to explain because it is just a chaotic process of decay,” she said.
But deeper understanding in recent years about the genetic and biochemical mechanisms that cause bodily functions to deteriorate mean that the accumulated damage caused by aging is no longer seen as inexorable.
“Researchers have come to realize just how malleable the aging process is. It can be ameliorated a great deal by drugs, genes, diet and exercise. It is clear that if you can target the underlying mechanisms of aging, which have become much better understood in the last couple of decades, you can stave off things that go wrong in later life,” Partridge said.
Indeed, the very idea of swallowing a pill to counter the effects of aging can seem like an alien concept.
Given the complexity of human aging, Partridge and her colleagues focused first on understanding aging in simple organisms, such as nematode worms, fruit flies and short-lived fish. Crucially, they have found that many of the genes controlling the process are conserved across species, including in mammals. What is more, experiments in mice show it is possible to slow down age-related damage not only by manipulating these genes but also through dietary and pharmacological interventions.
Now researchers from academia and the life sciences industry are trying to replicate these findings in people, with the goal of delivering longer and healthier human lives.
Two main approaches are being investigated. One involves repurposing existing off-patent drugs, such as the widely used diabetes treatment metformin or the immunosuppressant rapamycin. Intriguingly, both medicines seem to mimic the anti-aging effects of severe dietary restriction, which is known to delay aging in animals. The second strategy involves more blue-sky research and aims to restore health through cellular rejuvenation.
The work raises major questions for doctors, patients, investors, governments and wider society. Who will be eligible for future life-extending therapies? How much will they cost, and will they exacerbate existing health inequalities? How do you run effective clinical trials given the decades-long nature of aging? Will regulators ever accept biomarkers of aging as viable endpoints when aging itself is not defined as a disease?
The nascent field also faces a broader communications challenge. Given age-old fairy tales about finding the “elixir of life” and 21st-century techno-futurist fantasies of defying death, making the fundamental case for doing this research in the first place is not always easy.
“You often get a ‘yuck’ factor if you talk about preventing aging because people tend to think you mean transhumanism or something. Indeed, the very idea of swallowing a pill to counter the effects of aging can seem like an alien concept,” Partridge said.
“But it is important to realize that to a large extent we are actually doing this already because we already have millions of people, who are not ill, taking statins and blood pressure tablets over very long periods.”
She and other leaders in the field insist they are not chasing some dream of extending life to 150 or 200 years—let alone seeking immortality. Indeed, having old people live longer with low quality of life and becoming a greater burden to society is the last thing anybody wants.
“It’s extremely important to be very upfront about the real aim of increasing healthy life expectancy. We are looking for mechanisms that can help squash the period of ill health at the end of life, so it is very much a public health approach,” Partridge said.
The ethical and economic case for action is certainly strong. In the 70 years since 1950, the world population has tripled, while average life expectancy has shot up from 47 to 73 years. Yet healthy life expectancy has grown at a slower rate, leading to a widening gap between average lifespan and “healthspan,” or the period lived free from disease.
In 2020, the median gap between lifespan and healthspan was estimated at a daunting 9.2 years—a figure that translates into trillions of dollars of additional socioeconomic costs and untold individual suffering.
So, where are we now in the hunt for new interventions to compress this lifespan-healthspan gap?
There have been false starts, but the science is building steadily. Key discoveries include the pivotal role played by worn-out, or senescent cells, which are relatively rare when we are young but grow in number over the years and are implicated in many age-related diseases. Developing drugs to clear these cells is a growing focus for many biotech companies.
Average life expectancy has shot up from 47 to 73 years [since 1950]. Yet healthy life expectancy has grown at a slower rate, leading to a widening gap between average lifespan and “healthspan,” or the period lived free from disease.
Other approaches are being investigated in tandem to remove different molecular garbage that builds up as we get older in order to improve the function of organs around the body, from the brain to the eyes to the heart. Meanwhile, a separate tack is being taken by scientists who think getting rid of bad stuff is not sufficient and rejuvenation of cellular and immune system processes is key.
Overall, the US government’s database of ongoing clinicals lists more than 500 studies currently under way into healthy aging. There has also been a steady uptick in investment, with around $2 billion in venture capital invested in 2021 in companies developing anti-aging therapies, according to Longevity Technology, a research and investment platform.
Last year, that number was eclipsed by one single company when Altos Labs raised $3 billion for its launch, making it the best funded start-up biotechnology company of all time. It hopes to address the aging challenge at a fundamental level through cellular rejuvenation programming, inspired by the pioneering work of Nobel prize-winner Shinya Yamanaka, who showed in 2006 that it was possible to return cells to a pliable, immature state.
Partridge welcomes the breadth of current research, especially as the complexity of aging means that a “polypill” approach is probably going to be needed. But she is impatient for answers.
“There are lots of start-ups and a lot of investor money looking for somewhere to go—and that’s positive, since while some of these ventures will fail, others will succeed,” she said.
“But there are lots of other ideas that have come up from basic science that still need translation. We need money and people to crunch through this stuff quickly and to find out what is going to work. What this field needs badly is a clinical success story.”