Cutting-edge science seeks treatment for age

DRUGS, DIETARY SUPPLEMENTS MAY BE USED TO HELP THE BODY TO WITHSTAND TIME

It's one of the curiosities of the COVID-19 pandemic. In much of Africa, amidst widespread poverty and with a limited health-care infrastructure, the pandemic has actually taken less of a death toll than in rich countries like Canada.

The reasons for that seeming contradiction are not yet totally clear, but Colin Farrelly points to one likely explanation: the continent's markedly youthful population.

The coronavirus's fatality rate rises dramatically with old age, meaning that 88 per cent of the deaths in Canada have been among people 70 and over. The average life expectancy in sub-Saharan Africa is less than 62; in Canada it's 82.

“The COVID-19 pandemic is a highly fatal pandemic largely because of population aging,” notes Farrelly, a Queen's University professor who has a new journal paper on the topic.

“Our success in delaying death in late life made us vulnerable to COVID-19 mortality.”

In fact, some scientists are calling COVID the world's newest disease of aging, joining traditional culprits like cancer, heart ailments and Alzheimer's.

More intriguingly, and hopefully, Farrelly and others say the pandemic is a compelling reason to double down on a fascinating new domain of medical research. Its goal, rather than finding cures for individual diseases, is to treat the aging process itself.

Old age makes humans vulnerable to a range of killers, now including the novel coronavirus. Finding a way to slow down or reverse the aging process will protect people not just from traditional foes like diabetes and hypertension, but infectious diseases such as COVID-19, the thinking goes.

“It's a very hot area,” said Steven Austad, a biologist at the University of Alabama at Birmingham. And COVID-19, he said, is “focusing attention on it.”

“I think of it as 21st century medicine, as opposed to 20th century medicine, in which there were these silos of people who treat your heart, people who treat your lungs, people who treat your brain,” Austad said. “(Now) they've started talking to each other.”

Targeting aging, argues Farrelly,

“ought to be the major public health goal of the 21st century.”

What anti-aging scientists are pursuing is not the lifestyle fixes long proven to lessen disease risk, like regular exercise and a healthy diet. Instead, they're searching for drugs and dietary supplements that could actually tweak human biology to better withstand the ravages of time.

Part of that involves reverse-engineering long-lived humans and other animals to divine their molecular-level longevity secrets. Austad's lab, for instance, is studying ocean quahogs, clams that live to a remarkable 500 years. His focus is on a single muscle of the moluscs that keeps working through the centuries on a crucial task. It opens and closes the clam's shell, allowing food and oxygen to enter and waste to leave, while keeping predators at bay.

The key seems to be that the animal somehow avoids the clumping together of protein on the shell-opening tissue, a factor for humans not just in muscle ailments, but neurological diseases like Parkinson's and Alzheimer's, too, Austad said.

Meanwhile, experts like him stress there are already relatively cheap and safe drugs prescribed for other uses that have great potential as anti-aging agents. They include rapamycin, used now to combat organ rejection in transplant patients, and metformin, a diabetes medicine.

Other medicines are being developed to kill off damaging “senescent” – or zombie - cells which accumulate with age.

There is even science looking at whether transfusions of young blood could curb the ill effects of advancing years.

“Nobody has run away from aging by dieting and exercising,” says Alex Zhavoronkov, a Canadian biotech entrepreneur focused on longevity. “You don't see 120-year-old yogis with no wrinkles and perfect, youthful faces …To change the paradigm, we need to look at pharmaceuticals.”

Underlying the research are some cold, hard facts about human biology. Evolution, it seems, has ensured humans live healthily long enough to reproduce and look after their offspring until they become independent.

That translates into an average “biological warranty period” of about 70 years, the time before which the body begins to undermine itself, increasing the risk of disease and frailty, says Farrelly. So as we've learned to at least manage diseases of old-age and get people to live longer, the result is often years of illness and disability at the end of life, he said.

But that's not to say that growing old and weak in the way we expect is written in stone.

“There's no law of physics or law of the universe that says that aging has to occur,” said Austad. “Living organisms are almost definable by their ability to repair themselves … Aging is the ultimate failure of repair. (But) that doesn't mean it's not possible to intervene in the system.”

Such intervention would not necessarily extend lifespans, but ideally make the later years healthier and more productive, a major advance in itself.

“That would change the nature of human existence incredibly,” said Austad. “If you had another 10 to 20 years of healthy life to look forward to, that might influence almost everything you did – when you went to school, when you had kids, how many careers you had.”

Rapamycin may be the most promising of possible anti-aging treatments.

After it was discovered in the soil of Easter Island in the 1960s, Canadian researchers at Ayerst Pharmaceuticals found it had fungal-fighting properties. It eventually was approved as an anti-rejection drug. What has been learned about it since suggests it's “one of the very brilliant molecules that nature made,” said Zhavoronkov, founder of Hong Kong-based companies Insilico and Deep Longevity.

Numerous studies have found that feeding mice the drug dramatically increased their lifespans, and cut the risk of cancer and an Alzheimer's equivalent. Research has found cancer-preventing effects in human transplant patients, and increased resistance to influenza and better response to flu vaccines in older people. There was even a recent paper suggesting rapamycin applied to the skin reduces wrinkles and sagging.

“The overwhelming evidence suggests that rapamycin is a universal anti-aging drug,” wrote Dr. Mikhail Blagosklonny of Buffalo's Roswell Park Cancer Institute in a 2019 paper.

It should be administered under a doctor's supervision and tailored to individual recipients, he said, but “the time is now.”

Inexpensive and safe metformin is the subject of a major trial in the U.S. to determine if the treatment for type-2 diabetes can also more generally lessen the deleterious effects of aging, as found in many diabetics who took it. The study is led by Dr. Nir Barzilai of the Albert Einstein College of Medicine, who's also examining centenarians for clues to long, healthy life.

For Zhavoronkov, the burgeoning longevity-medicine field is not just about making old age healthier, but an economic imperative, too. As people last longer, with generally bad health during their final years, the cost of health care and social services for them will bankrupt some governments, predicts the author of The Ageless Generation. “We will have to relive something like the 1930s and 1940s if we do not control the aging spiral and death spiral.”

The trillions of dollars governments have spent on the fallout from COVID-19 – with its disproportionate burden on the elderly - drives home the point, he argues.

So how soon before a drug arrives that brings, not immortality exactly, but a longer “healthspan”?

Austad believes it is coming within 10 years. Zhavoronkov is also optimistic, saying the last decade has seen remarkable progress, “more discoveries in aging medicine than in the entire human history.”

It feels personal to Farrelly, a political-studies professor who monitors geriatric science. His mother died in the midst of the pandemic after years of battling cancer, unable to see family in the last three months of her life because of COVID protocols. But he's hopeful.

“I believe it will happen in my kids' lifetime,” said Farrelly. “They won't age like my mother did.”

PETER J THOMPSON / NATIONAL POST It's not just the age, but rather the frailty of older people that make them more vulnerable to illness and the ravages of the viruses that we're seeing in the pandemic. There is a drive to treat that aging process itself.