Although Johnson’s research has led to drug development to slow the effects of age-related diseases, he has yet to find the secret to stop aging. Now the soft-spoken redheaded scientist is running out of time as he confronts his own mortality.
Five years ago, at age 66, work got confusing for Johnson, a professor in the Institute for Behavioral Genetics at the University of Colorado at Boulder. He found it impossible to keep track of his many projects. He began wondering whether he had Alzheimer’s like his newly diagnosed sister.
He spoke to his wife, Vicki Simpson, about the little dogs he frequently saw running around the house (even though he knew they weren’t real). Simpson, a retired anesthesiologist, later learned such hallucinations are a trademark sign of Lewy body dementia.
At first, she praised his imagination and then after several months suggested they visit a memory clinic. There he was diagnosed with probable Lewy body — a fatal disease with inescapable dementia that can be diagnosed with certainty only at death. Right now, there is no cure, only ways to ease symptoms.
According to the Mayo Clinic, Lewy body is the second most common progressive dementia after Alzheimer’s. Protein deposits (called Lewy bodies) develop in the brain nerve cells responsible for movement, thinking and memory.
“His foundational knowledge on aging is still strong, but it’s difficult for him to pick up new techniques on the computer, for example,” Simpson says. Her husband’s motor control is declining and word finding is more of a struggle. His gait is slow and somewhat similar to Parkinson’s. The occasional tremors in his left arm are worsening, “but not so bad I’ll quit working,” he insists. No longer being able to drive is the most frustrating limitation.
Johnson still speaks daily with colleagues or visits his lab at the university. “It seems more important to make modest gains within a time frame that can help me,” he says. He looks out for his health, taking tennis lessons with his wife. And he joined her at the vegan table — well almost. His face is deadpanned and then breaks into a grin. “I have a hamburger every couple of weeks,” he admits.
“I think I have gained health within that [plant-based diet] framework,” he says, “even if it can’t retroactively change my Lewy body.”
And while he considers diet and exercise major contributors to our health, he says we also need modest amounts of stress to build resilience against all the factors that chip away at it.
Johnson, who has a long list of honors and published research, continues to work in his field because he believes challenge is healthy. He is a founder of a company, Cirque Cryotech, which was started last fall. Its aim is to extend the shelf life of frozen organs before transplantation.
Together with his team at the University of California at Irvine, Johnson identified the first gene that affects aging: age-one. Even more important, Johnson says, was that age-one is a part of the insulin signaling pathway, common in several species including humans, responsible for the rate of aging.
By manipulating this one gene, Johnson and his graduate student, David Friedman, were able to lengthen the life of C. elegans from 20 days to about 35 days — a life extension of 70 percent. Previous research had only found roundworms to live longer through caloric restriction. But Johnson’s worm ate well.
Johnson hypothesized that if about 80 percent of the genes in the nematode (or roundworm) function similarly to those in humans, a mutation of a similar longevity assurance gene in humans could dramatically lengthen human lives.
“Identifying a specific gene is harder than finding a needle in a haystack, it’s a needle in a haystack of needles that aren’t marked,” Johnson, now 71, says jokingly.
Soon after the discovery, Johnson was interviewed on NBC Nightly News’ special segment on aging. He was featured in Life Magazine, Newsweek, Men’s Journal and Scientific America.
“It wasn’t until my dad read about my work in Reader’s Digest that he believed I was doing something worthwhile,” Johnson says with a grin.
When he entered the field in the mid-1970s, research on aging wasn’t well supported. Many scientists thought anyone who claimed to be able to slow the aging process or extend life was a fraud.
He faced conflicting responses when his paper on the discovery of age-one was published in 1988 in the journal of Genetics. The scientific old guard insisted something was wrong with his experiments. Entrepreneurs called Johnson wanting to exploit his science, prematurely, to make money.
“I sought independence over money,” he says, explaining why he eventually returned to his home state to work at the University of Colorado. For someone who loves the mountains as much as his work, living in Colorado with his wife to raise their three redheaded kids was a worthwhile trade-off.
He has spent his whole life measuring trade-offs and asking: Nature or nurture?
“That’s the question I’ve been asking most of my career,” Johnson says, smiling and raising bushy eyebrows. “Instead of asking which is more important, we should ask how they best synergize.”
Pursuing that synergy has led science to powerful interventions to control aging, Johnson says. Drugs have been developed to slow the symptoms of Alzheimer’s and the effects of age-related diseases such as diabetes, Parkinson’s, pulmonary fibrosis and cancer. Metformin, a drug used to treat Type 2 diabetics, helps modulate the insulin pathway. It is now being tested as a possible anti-aging drug in clinical studies approved by the Food and Drug Administration.
“Thirty years ago, the FDA would never have considered doing a human clinical trial with potential ‘anti-aging’ drugs,” Johnson says. People now question if senescent (gradually deteriorating) cells, also known as zombie cells, have an important role to play in aging. These cells have stopped dividing and instead secrete substances harmful to healthy surrounding cells.
Johnson is working on new funding to develop senogenic drugs. These “exfoliating-like” medications lengthen the life of mice by eliminating dead cells.
“People wouldn’t be studying the impact of modulating a single cell type (in this case senescent cells) if Johnson hadn’t made it clear 30 years ago that by manipulating a single gene we could impact aging,” says Jim Cypser, Johnson’s friend, business partner and frequent chauffeur now that Johnson cannot drive.
Even though he has devoted his career to slowing down aging, Johnson believes in extending the health span (quality of life), not necessarily the life span (quantity).
“I’d much rather live a shorter but healthy life as opposed to living an extra 10 years locked into a chair not being able to participate.”
He thinks he might have a decade left to live but assisted suicide is something he has seriously considered if he becomes incompetent. But then, he asks, how do you measure competence?
“I’d much rather see my kids and grandkids and then end it, rather than wait and hope that they come by the nursing home,” Johnson, who has one grandchild, says. “It’s too bad that society doesn’t have a leaving ceremony before death instead of a funeral.”
Johnson and Simpson live in Louisville, Colo., where they make themselves keenly aware of passing time. Several clocks chime and cuckoo in their home every hour.
“We are counting the amount of daylight gained each day,” he says.
When asked to reflect on life’s most breathtaking moment, Johnson does not name finding the gene that made him famous.
“It was the birth of my first child,” he says.
No matter how many years he has left to live, Johnson says he believes his life is extended through the lives he has loved.
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