Who wants to live to be 150? Well, lots of people, probably. But while a long life of good health, good spirits and physical activity is worth living, few would opt to extend a life that is full of age-related disease and disability.
“What we want is to live longer, healthily,” Steven Austad, Ph.D., said, speaking at a recent course on the biology of aging at the MDI Biological Laboratory on Mount Desert Island. And since the average human lifespan in developed nations has increased steadily since the year 1900 at a rate of about 6.5 hours per day with no sign of abating, he said, “there is no obvious limit to human life expectancy.”
In fact, Austad is so confident that he’s made a small wager with a colleague that someone already alive today will live to celebrate his or her 150th birthday. They have each invested $150, counting on the value to reach $500 million by the year 2150. Austad said he expects to win the pot for his heirs.
But a longer lifespan doesn’t equate with a longer healthspan, he cautioned.
“Because we’re getting so good at delaying death, we face a future of increasing misery,” Austad said, unless science finds ways to eliminate, delay and compress what are now considered “normal” processes of aging. And meaningful progress is already being made, he said, as scientists identify specific, inactive genes that, when “switched on,” extend the lifespan of common research animals such as the tiny c. elegans roundworm, fruit flies and mice.
“We have identified hundreds of genes that do this,” he said. “And each time we find a gene that extends the life of one of these animals, it gives us a potential drug target to do the same thing in humans.”
Austad, who is 69, chairs the biology department at the University of Alabama at Birmingham. He was one of several featured speakers during the two-week course “Comparative and Experimental Approaches in Aging Biology Research,” hosted by the MDI Biological Laboratory and developed in partnership with The Jackson Laboratory, a larger genetics research institution with campuses in Bar Harbor, Connecticut, California and other locations. The event brought together more than 20 leading researchers and 20 students from across the country and internationally to share the most promising methods and ideas on the forefront of studies in aging.
Austad’s own research focuses on the question of why animals, including humans, age. Why do fruit flies live only a few days while ocean quahogs can live 500 years or more? Why do mice live about two years while some whales lives 80 or 90 years or longer?
“There are many animals out there much better at resisting aging than others,” he said. “We should study them and learn how they do it.”
But a longer life is not enough. Already, average human life expectancy in developed nations has risen from 50 years in the early 1900s to 79 years now, he said, thanks to advances in lifestyle, nutrition, medicine and other factors. But longer lives are associated with increased risk of age-related diseases, including pneumonia, diabetes, stroke, cancer and dementia.
Studying individual diseases is one way to maintain health over a long life, he said, but “the 21st century approach is to look for the underlying cause, and the primary one here is aging … If we can treat the underlying cause, there is every reason to think we can delay the onset of all these diseases.”
Switching on resilience and regeneration
Delaying aging through building resilience is one approach to lengthening the human healthspan. Another is enabling human cells to reproduce and regenerate tissue the way some other animal cells do. Starfish are a familiar example, but salamanders, fish and many other animals routinely regrow tissue that is damaged through age or physical trauma.
“Nature is filled with animals that regularly regenerate or regrow body parts. It’s more the norm than not,” MDI Biological Laboratory president Kevin Strange, Ph.D., said.
For example, a newborn mouse, whose genome is nearly identical to a human’s, can regenerate up to 70 percent of its heart tissue over the course of a few weeks.
“But if you have a heart attack, you don’t regrow that tissue,” Strange said. “What we are asking is how do they do it, and why can’t we do it? They don’t have special genes that we don’t have; it’s the same thing. We need to develop drugs that activate that capability in humans.”
Already, Strange’s lab has identified a molecule that stimulates heart tissue regeneration in both zebrafish and adult mice. It shows promise for eventual use in humans. But Strange cautioned that developing a comprehensive knowledge of the biological processes that underlie both resilience and regeneration is essential to the success of any pharmacological therapy.
“If you’re a mouse who has had a heart attack, you’re in good shape,” he said. “But the goal is to develop a treatment for humans, and that’s a long, hard, very expensive road.”
Learning from animal models
Faculty researcher and course organizer Aric Rogers, Ph.D., of the MDI Biological Laboratory said a similar course last year focused more on the specific mechanisms of cellular regeneration and resilience, while this year’s event was directed toward familiarizing young researchers with a variety of animal models.
“Humans are not particularly good at regeneration, but a lot of animals are really good at it,” Rogers said. “The goal here is to open up the research and understand what is happening in multiple [animal] model systems,” he said.
Students and faculty took part in the course from Finland, Germany, Australia and other countries as well as the U.S. Tuition was $4,000, offset by fellowship funding. Individual classes addressed basic mouse genetics, data analysis, the genetic impact of dietary restriction, the merits of invertebrate versus vertebrate research animal models, and other topics.
Hakan Tarakci, a 23-year-old graduate student at the Australian Regenerative Medicine Institute, was attracted by the opportunity to learn about a variety of research animal models.
Most researchers at ARMI use the zebrafish, a mainstay of biomedical research labs around the globe, he said, looking up from dissecting a minute African turquoise killifish under a microscope.
“No one at ARMI uses c.elegans or these other species,” he said. As a vertebrate, the killifish is valued for its relatively short natural lifespan, which enables scientists to study its entire life cycle over just a few months.
Ee Phie Tan, a 28-year-old from Malaysia finishing her Ph.D. at the University of Kansas Medical Center, is studying the ways in which protein modification affects the function of the mitochondria, an intracellular structure responsible for energy production that supports neuron signaling. That signaling declines with age and may be linked with Alzheimer’s disease, Parkinson’s disease and other age-related conditions.
Tan has been using human cell lines in her research.
“The human cell line is only a tool for studying the molecular mechanism,” she said. “But here we can manipulate the animal model, see if it gets more sick or healthier, see how it affects health and lifespan.”
And 38-year-old Michael Stout, Ph.D., who is finishing a postdoctoral fellowship at the Mayo Clinic in Minnesota, said the course provided important alternatives for studying gender-linked differences in metabolism and aging.
It’s more efficient to study short-lived animal models such as c. elegans, he said, “and you can garner information that is very translatable to higher-order species more aligned with humans.”
MDI Biological Laboratory was founded in 1898 as a summer marine research station. In 2000, it became a year-round organization. Strange took leadership in 2009 and developed a more focused mission in regenerative and aging biology and medicine.
Strange said there is a lot of excitement in the research community about the potential to stave off aging in humans.
“All the machinery is there to do it,” he said. “We just have to figure out a way to get it working.”