Sel Yackley is a busy woman.
She makes jewelry, sings in a choir and knits hats and scarves for the homeless. She also reads with her book club, goes to the gym a few times a week and is active in several civic organizations. According to her Fitbit, she still manages to sleep an average of 7½ hours a night.
At 85, Yackley is a “SuperAger.” That is, someone who is 80 or older and retains the memory capacity — based on delayed word recall testing — of a person at least two to three decades younger.
Dr. M. Marsel Mesulam, who founded the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at the Northwestern University Feinberg School of Medicine in the late 1990s, first defined a SuperAger. Mesulam Center researchers reflected on a quarter-century of SuperAger study in an analysis published Thursday in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Yackley, who is among the nearly 300 people who have participated in the Northwestern University SuperAging Program (NUSAP) since 2000, is proof that impaired memory isn’t always a hallmark of aging.
“We are going to be role models for other people who are getting older,” she said. “Take good care of your health and eat right and be sociable.”
Is SuperAging genetic?
Yackley, a longtime Chicagoan who hails from Turkey, acknowledges that genetic factors may be contributing to her youthful cognition. Her mother and father lived to be 86 and 88, respectively. On the other hand, Yackley feels her joie de vivre helps keep her mind sharp.
“I think it’s partly your determination to live a long life and your activities that enable you to do so,” she said, encouraging older adults to pursue “things that make you proud.”
Yackley’s peers in the SuperAger program share a spirit of connection, according to Tamar Gefen, a co-author of the analysis and an associate professor of psychiatry and behavioral sciences at the Feinberg School.
“I don’t know if it’s necessarily social connections, it’s just connections in general,” Gefen said. “There are people who are connected to the land, there are people who are connected to their ancestry, people who are connected to their grandchildren, who are connected to their art.”
Gefen added, “You don’t see a lot of detached SuperAgers.”
That said, people can’t simply will themselves into “superaging.”
More than 7 million people in the U.S. are living with Alzheimer’s disease, according to the Alzheimer’s Association, a statistic that’s projected to soar to nearly 13 million by 2050. About 1 in 9 people 65 and older have this most common form of dementia.
At age 45, the lifetime risk of developing Alzheimer’s is 1 in 5 for women and 1 in 10 for men. SuperAgers are defying these odds.
“Genetics is a part of it, definitely,” Gefen said. “We know that there are major risk genes for Alzheimer’s disease, and SuperAgers don’t have those genes.”
For example, research has shown that people of European descent with two copies of a gene called APOE4 have a 60% chance of developing Alzheimer’s by age 85.
“My interest is, are there genes that SuperAgers harbor that can actually protect them against getting Alzheimer’s disease?” Gefen said. “And is there a gene, let’s say that’s related to the immune system, that is over-expressed in SuperAgers that can be manipulated to then help individuals protect themselves?”
As she continues searching for such answers, Gefen said her team’s most exciting findings have stemmed from the brains of SuperAgers who have died.
SuperAgers’ brains may be built differently
Gefen and her colleagues at the Mesulam Center have autopsied nearly 80 SuperAger brains and compared them to those of their “neurotypical” peers. They focused on two indicators of Alzheimer’s: protein buildups in the brain called amyloid plaques and tau tangles.
“What we found in memory centers of the SuperAging brain is that there are a lot fewer tau tangles,” Gefen said. “But interestingly, amyloid or plaque pathology doesn’t really differ a whole lot.”
Because a number of Alzheimer’s treatments single out amyloid plaques, SuperAgers bring such treatment methods into question, Gefen said: “Are we really targeting the right target if SuperAgers and their peers have similar amounts of amyloid?”
Other findings include that SuperAgers tend to have larger entorhinal neurons, which are nerve cells that are key to memory, and more von Economo neurons, which are nerve cells critical to social behavior.
“Our guess is that [SuperAgers] are probably born with these kinds of structural protections,” Gefen said. “But we’re now going really deep into the molecular mechanisms of the cell in order to figure out what is keeping that cell strong.”
Dr. Timothy Chang, who wasn’t involved in the SuperAger research, works on the opposite end of the spectrum. An assistant professor of neurology at the Mary S. Easton Center for Alzheimer’s Research and Care at UCLA, Chang studies and sees patients who have dementia.
Analyzing “outlier populations” such as SuperAgers is valuable to the medical field, he said.
“Those cases are really interesting,” Chang said. “They can teach us a lot about how, potentially, those people, based on genetics or other lifestyle factors, were able to avoid the disease.”
SuperAgers live on in the lab
Yackley has toured Northwestern’s Brain Bank, where she is “proud” her own brain will one day be sent for study. She’s also making plans to donate the rest of her body to science.
“Hopefully, maybe my heart or my kidneys can be used for transplanting,” Yackley said. “I don’t want to be underground.”
In the meantime, Yackley would be grateful to make it to 90, she said. She maintains a to-do list and aims to log about 4,200 steps a day. The retired journalist, travel agent and memoir author is already at work on her next undertaking.
“I am trying to put together a scrapbook of my life, and that’s a big project,” Yackley said.
Though the prevalence of SuperAgers is unclear, they appear to be uncommon. Gefen and her co-authors noted that during the initial recruitment of study participants, just 10% met the criteria of SuperAgers. Today, 101 SuperAgers ranging in age from 81 through 111 are actively involved in Mesulam Center research.
Not all SuperAgers prioritize their health — on the contrary, some defiantly savor their vices — and many have lived difficult lives, Gefen said. But they don’t take their cognitive fitness for granted.
“These SuperAgers know that they have a gift,” Gefen said.
