Molveine Karan raised her arms steadily above her head, tapped her foot lightly against the floor as she moved her leg, and tilted her neck back and forth.
“If you don’t do it, you stiffen up like a board,” the 98-year-old said.
Karan was demonstrating her morning routine, which includes an hour of stretching and exercise. She does 20 repetitions of various leg, arm, hip and neck motions to keep her limber. After her stretches, she goes back to sleep for an hour.
I met with Karan one sunny Thursday afternoon. She greeted me at the elevator outside of her fourth floor apartment in South Brooklyn, smiled and walked me into her living room.
“I’d still be working if I could read,” said Karan, who suffers from macular degeneration. She can focus on nearby faces and see the ground beneath her feet, but that’s just about it. Luckily, macular degeneration and slight hearing loss — mitigated by hearing aids — are the only health problems that affect Karan’s daily life.
When it comes to meeting or exceeding the average life expectancy in the United States, which is 76 for men and 81 for women, most scientists agree that environmental factors like exercise and diet play a significant role. Israeli scientist Dr. Nir Barzilai, who started his Longevity Genes Project in 1998, contends that genes play a role, too, and that it’s just a matter of time before the effects of aging can be reversed synthetically. His test subjects: centenarian Ashkenazi Jews and their relatives.
Barzilai believes the secret to longevity lies in the genes of long-living Ashkenazis like Karan. One day, he hopes to manufacture drug therapies to mimic those genes associated with long life and resistance to classic old-age ailments such as Alzheimer’s, diabetes and cardiovascular disease.
To be clear: Ashkenazi Jews do not live longer than other people. Barzilai studies Ashkenazi Jews because of their unique gene composition. Geneticists prefer isolated groups, such as the Icelandic (“half a million people in Iceland are all children of four Vikings and five Irish women,” said Barzilai), the Amish and Ashkenazi Jews, whose move to Europe led to a bottleneck effect, which refers to a sudden reduction in the population. These groups trace their lineage back to a small number of common ancestors, resulting in a smaller gene pool. This makes it easier to identify genetic variants, such as those associated with particular diseases or longevity, because there are fewer variants to study.
The additional cultural factor that makes Ashkenazi Jews good study subjects? Their relatively similar socioeconomic statuses.
“That’s very important,” said Barzilai, “because the diversity in health care is associated with education and income.” With Ashkenazi Jews he can control for many outside variables and focus on the genetics.
For most people, environment determines health in old age. It breaks down to 20% genes and 80% environment, according to Barzilai’s estimate. But it’s possible that for people like Karan, genetics play a much larger role.
“My husband was a physician, so I didn’t eat right, didn’t exercise,” she said, smiling. She said she owes her long life to genes. In fact, she only started her morning stretching routine about a dozen years ago, when she was in her late 80s. Her father died at 56, but her mother lived until she was 80.
With research subjects like Karan, Barzilai and his team have made significant findings over the 17 years of the study. They found that healthy centenarians had very high levels of HDL cholesterol, or “good” cholesterol, which removes another type of cholesterol that can cause clots, LDL cholesterol, from arteries. In comparison with the rest of the population, the centenarians had nearly double the amount of HDL.
As a result, Barzilai found two genes that regulate HDL cholesterol. First is CTEP gene, which protects against cardiovascular disease, Alzheimer’s and Type 2 diabetes. Second is the APOC3 gene, which protects against diabetes and heart disease. He also found a third gene associated with healthy longevity, the ADIPOQ gene, which protects against diabetes and inflammation.
In other words, most centenarians have high HDL cholesterol and several if not all of these genes — which is why Barzilai hopes to develop a drug therapy treatment that imitates the “longevity genes” to ensure a healthy long life.
“We can sequence the whole genome of all the centenarians in the control [group] and find the mutation that is associated with longevity,” he explained.
Geriatrics specialist Dr. Richard Besdine, professor of medicine at the Alpert Medical School and professor of health services policy and practice at Brown University, sees people like Karan as exceptions to the rule.
He stands by classic doctors’ orders: Physical exercise and a healthy diet will serve patients best. Besdine, who is in his 70s himself, plays squash regularly with his medical students to stay healthy and fit. He said 30 minutes a day of aerobic exercise should do the trick. Even walking is better than nothing.
As for diet, Besdine sticks to the Mediterranean Diet: lots of vegetables, olive oil, some red wine and no red meat.
He doesn’t believe that old age can be cured like a disease. “Aging defined as a disease? No,” he said, “But aging defined as a time of increased vulnerability? Of course.”
Besdine agreed with Barzilai that the most important breakthroughs would concern the treatment of old age diseases, rather than longevity outright. After all, nobody would want to live to 100 if he or she were to be stuck in a hospital bed for the last 20 years.
However, the two men differ in their proposed ways of dealing with growing older. “I deeply believe that understanding fundamental processes of aging at a molecular and genetic level is likely to lead to breakthroughs,” Besdine said. However, he preferred a more hands-on approach that would help the majority of people now, as opposed to a miracle pill that would affect the elderly many years in the future. “Nobody should sit around drinking Frappuccinos… looking for the remote in their sofa cushions, [while scientists are] looking for a molecular genetic solution to old age.”
But recently, Barzilai has come one step closer to finding just such a solution, Nature reported in June. The Federal Drug Administration discussed approving a clinical trial called Treating Aging with Metformin. Together with a group of scientists, Barzilai wants to investigate the effects of this drug, which has been used by people with Type 2 diabetes for over a half century, on 3,000 people (ages 70 to 80) over the course of five to seven years.
Metformin has been proven to suppress glucose production by the liver and increase sensitivity to insulin, and has been shown to extend a healthy lifespan in worms and mice. Which makes Barzilai and others hopeful that it might delay heart disease, cancer and cognitive decline in humans.
“This is very important because it is not about the specific drug. It’s about having aging being a target for treatment,” said Dr. Barzilai. “So far the FDA doesn’t think that aging is something you can intervene with.” But that might change soon.
Rachel X. Landes is a Forward Summer Fellow. Contact her at firstname.lastname@example.org