Forever young? New breakthroughs are changing how we age

Scientists are finding ways to rewire our cellular machinery to repair the body and treat diseases of aging like cancer and diabetes.

Forever young? New breakthroughs are changing how we age

If you worry about the health risks associated with aging, this may alarm you: Every eight years, the average human’s risk of death doubles. At 30, Canadians’ odds of dying are less than one in 1,000, based on statistics compiled by the Human Mortality Database. By 65, when chronic diseases often creep in, it’s closer to one in 100.

But if that sets your yellowing teeth on edge, here’s a more hopeful stat: Every year in recent history, human life expectancy has extended by an average of three months. In 2020, the average Canadian lived to almost 82. Next year, that figure will likely be close to 83.

Improvements in nutrition, sanitation and education have played a massive role in adding decades to our lives over the last century. Now medical researchers and biotech startups are setting their sights on eradicating diseases like cancer, diabetes and cystic fibrosis. Drawing on such breakthroughs as the discovery of stem cells and the development of gene editing — along with advances in nanotechnology that make it easier to deliver therapies — they’re working to wipe out a host of debilitating conditions. Emerging treatments that effectively kill the killers could cause huge leaps in life expectancy.

Within the next few decades, the prognosis for people with many critical conditions will be very different, says Michael Sefton, scientific director of the University of Toronto’s Medicine by Design research hub, which receives funding from the Canada First Research Excellence Fund. “I’m sometimes accused of being a dreamer, but I can imagine the day when we’re seeing more effective treatments for cancer, heart failure, even neuro-degenerative diseases like Parkinson’s and Alzheimer’s. We’ll be treating the underlying causes of the diseases with regeneration-based therapies, not just symptoms.”

The new treatments will transform not only the quality of our so-called golden years, but the very notion of what it means to grow old. “The consequences will be profound and wide-ranging, for all of us personally, for our friends and families, and for society and humanity as a whole,” notes science journalist Andrew Steele in his recent book Ageless. “This is a hugely exciting time to be alive.”

But these treatments often face a powerful enemy — the body’s own immune system. We’re equipped with defences designed to destroy anything that seems out of place, like viruses and bacteria or mutated cells that could turn into cancer. The problem is that implanted stem cells and genetic therapies look like an invading army to the immune system, which has been primed over millennia to be trigger-happy. The result is the body kicks out the cure.  


Customizable repair and regrowth

A few key scientific breakthroughs ushered in this era of regenerative medicine. One of the most important was the discovery of stem cells, often described as building-block cells, which can develop into specialized types, such as muscle, skin or brain. Discovered in mice by Canadian scientists James Till and Ernest McCulloch in 1961, stem cells can help the body repair damaged tissues.

But harvesting them from animals or human embryos is controversial. So when Japanese scientist Shinya Yamanaka reprogrammed human skin cells and effectively reverted them to stem cells, he unlocked huge potential for medical advances. The groundbreaking 2007 discovery meant that — theoretically, at least — an unlimited number of stem cells could be produced from a patient’s own cells, eliminating the need for donations and reducing the risk of immune rejection.

“It opened up the field dramatically,” Sefton says. “And it made one think about what could be done if one had an infinite number of cells available at one’s fingertips.”


Rewriting the code

Genome editing — altering the genetic code in DNA — has taken off with the development of CRISPR technology. Gene editing can mend or replace the faulty genes that cause genetic disorders like cystic fibrosis, muscular dystrophy and sickle cell anemia. It’s also a promising way to fight cancer. Over the past five years, doctors have started using gene editing techniques to fine tune patients’ immune systems to make them more potent against their specific type of cancer. “Gene editing basically allows us to make cells that are better than what nature makes,” says Sefton.

But to be effective, gene-editing tools need to reach precise targets. In the case of cystic fibrosis, once the tool gets into the cell nucleus, it must locate a series of about 20 DNA letters that mark the spot of the mutation that causes the disease — out of three billion letters in the human genome.

That’s only part of the challenge. Getting the fragile strands of mRNA that are used in gene editing into the right cells without being damaged requires feats of engineering on the tiniest of scales. To help the tools reach their targets, new therapies under development are drawing on innovations in nanotechnology — specifically lipid nanoparticles (LNPs).

These tiny spheres made their mark by delivering the active ingredient in mRNA COVID-19 vaccines. They function by protecting therapies in a shield of fatty molecules and helping them find and enter target cells. Most LNPs have limited reach and successfully enter only a handful of cell types, usually in the liver or spleen. But researchers have designed an inhalable version that could be used to deliver gene therapies directly to the lungs.

Bowen Li, an assistant professor at the University of Toronto who collaborated with colleagues at MIT on the inhalable LNP, sees real potential in this development. “This lipid can enable us to deliver mRNA to the lungs much more efficiently than any other system reported so far,” explained Li to MIT News.

Leo Chou, a scientist at the University of Toronto, is also working at the tiniest of scales. He says that researchers already have a basic understanding of how assemblies of proteins and nucleic acids function in our bodies. He calls these “molecular machines” and believes that we could one day create synthetic versions that could interface with naturally produced ones. “If we can miniaturize the machines at that level, then we have lots of new opportunities to diagnose and treat diseases,” he says.

One treatment under development at his lab uses nanostructures made of DNA, which can be programmed to deliver one or more molecules in precise patterns that provoke a more potent immune response, and could one day be used to create targeted vaccines for diseases like cancer. “It’s all about disruptive changes to the way drugs are delivered,” he says.


Protecting the body from itself

Dozens of research teams across the country are looking at ways to tackle one of the biggest chronic diseases: diabetes. Scientists estimate it might take another five to 10 years of development, but if even one of the emerging therapies is successful, it could effectively bring an end to the disease, an outcome that had seemed inconceivable.

Type 1 diabetics, whose bodies aren’t able to produce insulin, face a lifetime of costly, time-consuming injections — and heightened risk of heart attacks, stroke and kidney failure. Attempts to treat the disease often rely on transplants of healthy, insulin-producing cells, but the patient’s immune system typically attacks the implanted cells. Successful transplants come with a trade-off: the patient spends the rest of their life on immune-suppressing drugs.

But progress is happening: A team of diabetes researchers at University of Alberta reported early success in 2022 in a first-in-humans clinical trial to test whether pancreatic cells grown from stem cells could be safely implanted and begin to produce insulin. Their next goal is a transplant that doesn’t require immune-rejection drugs. Also at the University of Alberta, immunologist Colin Anderson is working on techniques to effectively reset the immune system by removing problematic cells, thereby preventing it from attacking insulin-producing ones.

And researchers at Allarta, a biotech startup based in Hamilton are developing a protective structure that shields the transplanted cells from being destroyed by the patient’s immune system. Co-founder and chief operating officer Maria Antonakos likens the company’s synthetic hydrogel to a shark cage. “What’s inside it is protected from immune attack,” she says.

Allarta hopes to begin clinical trials by 2025. What makes its therapy even more exciting is that, like many of the new treatments and interventions targeting serious conditions, the hydrogel innovation is a “platform” technology that can be applied to other diseases, like Parkinson’s and hemophilia.


The age of agelessness

Breakthroughs like these have the potential to bring about dramatic changes in our lives. As more conditions become treatable and even cured, people will stay healthier longer. Remember those ever-expanding life expectancies? While you read this article, they increased 90 seconds.

As disease disappears and we live longer, healthier lives, we’ll stop talking about lifespans and refer to healthspans instead. Many areas of our lives will be ripe for reconsideration, including how we work. Why not start a new career at 50, if you know you have decades more to live (and decades’ worth of living expenses)? Pension funds will need to alter their long-range forecasting. Hospitals will focus on crisis-care rather than chronic illnesses. And doctors will be more holistic and prevention-focused. “It’ll be more of a checkup, like going to the dentist,” says Steele.

All of which raises questions about equity and how we ensure the benefits are distributed fairly. “It’s important to get diverse communities involved in discussions about the future of medicine now,” Sefton says, “to ensure the new preventative treatments are accessible to all.”

Ultimately, the end of disease, combined with other scientific advances that could one day prevent our cells and organs from deteriorating as we get older, could usher in a new era of agelessness.

Ask Steele to estimate at what age human life expectancy will top out, and he can’t. “I don’t believe there’s an actual limit,” he says. “I would be shocked if I came back to life in 2500 and saw that people were still dying of the diseases associated with old age.”

Photography: Neil Ta