Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

The centenarian gender gap is just one of the mysteries researchers hope to solve with new studies.

The gender gap is alive and well where it concerns living to at least 100 years old.

Women make up 75% of the 550 Ashkenazi Jews, age 95 and up, examined in the Longevity Genes Project (LGP) at Albert Einstein College of Medicine of Yeshiva University, which since 1998 has sought to identify genes connected with longer life. That percentage rises to 85% in the New England Centenarian Study (NECS), the world’s largest study of centenarians with 1,600 enrolled, plus family members.

Nir Barzilai, M.D., LGP’s lead investigator, told GEN that in LGP some of that male presence reflects the fact the study only examines women who have had children in order to assess genetics across generations, yet numerous centenarian women worldwide have never had children.

How does the dominance of women in the study group affect other findings of the major studies—for example, the overall pleasant nature of centenarians found by LGP and NECS?

Personality Changes

Dr. Barzilai says there are two possible explanations. One is that women who made it to 100 were enabled in doing so by their personalities. Yet many seniors with positive attitudes still pass away in their 60s, so personality may not be as important in promoting healthier aging as once thought.

“The second possibility, which I think is more likely, is that while people think that personality doesn’t change with age, and maybe it doesn’t between 18 and 70, I think it changes with age,” Dr. Barzilai said. “When I talk to some of the kids and I say, ‘Your father is such a nice guy,’ they’ll tell me, ‘You should have seen him when he was 80. He was a sonofabitch.’”

“I think there are a lot of changes in personality with aging. So that’s what we find,” he added.

It is not known how personalities change: How likely is it for people to change from disagreeable to more pleasant, and how often vice versa? Also unknown is how the personality differences break down by gender.

LGP was the source of a study published May 21 in the journal Aging, which connected genes for longevity to personality traits such as being outgoing, optimistic, easygoing, and enjoying laughter, as well as staying engaged in activities.

Contemporary Wisdom Defied

In addition to LGP, Dr. Barzilai leads the LonGenity research study, which validates genetic findings in offspring of parents with exceptional longevity vs. offspring of parents with usual survival.

LGP found only 5% of its centenarians linked religious faith to their longer life—a finding at odds with other studies linking religious faith to physical health and stress coping ability in people living past 100: “It’s interesting, because I’m thinking, if I get to 100, I’ll say, thank God.”

Another finding from Dr. Barzilai’s research defies contemporary wisdom: Not all centenarians live the healthiest lives.

“We have a woman who was 110 years old when she died, and she smoked for 95 years. And 50% of the centenarians were overweight or obese. And less than 50% of them were doing moderate exercise; I’m talking walking or cleaning the house. And only 2% are vegetarian,” Dr. Barzilai said.

Among LGP’s findings: 27% of women and an equal percentage of women in the general population attempted to eat a low-calorie diet. Among men, 24% consumed alcohol daily, compared with 22% of the general population. And only 43% of male centenarians reported engaging in regular exercise of moderate intensity, compared with 57% of men in a control group.

While far more women than men may live to the century mark, the men who make it that far or farther are often healthier. Thomas T. Perls, M.D., MPH, founder and director of NECS, told GEN a probable reason is that women handle age-related diseases better than men do.

“The double-edged sword of that is that they then live with their diseases, whereas men who get such diseases quickly die from them. So for men to reach these ages, they have to be in really spectacular shape,” Dr. Perls said.

More Research

Earlier this year, NECS published findings from sequencing the whole genomes of two “supercentenarians” older than 114 (one female, one male). The findings, published in Frontiers in Genetics of Aging, found the centenarians had a comparable number of known disease-associated variants relative to most human genomes sequenced to date, and did not appear to have most well-established human longevity-enabling variants. Moreover, 1% of the centenarians’ longevity variants were previously unseen, and may lead to new genes involved in exceptionally long life.

The centenarians were two of 801 examined last year in a now-retracted Science study corrected and re-published in January in PLoS ONE. That paper found that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. While variants of two specific genes (LMNA and WRN) were linked with premature aging syndrome, at least one variant could be associated with slower aging and decreased survival.

“The next steps are to take that variant and study it with functional studies,” said Dr. Perls, who is also an associate professor of medicine at Boston University School of Medicine and a practicing geriatrician at Boston Medical Center.

Dr. Perls is helping gather centenarians willing to have their genomes sequenced by research teams vying for the $10 million Archon Genomics X PRIZE, presented by Express Scripts. The nonprofit X PRIZE Foundation will reward the first investigator team that most rapidly, accurately, and economically sequences 100 whole human genomes from centenarians living in and outside the U.S. Dr. Barzilai heads a consortium supplying the 100 genomes.

[Click here to watch a video in which thought leaders like J. Craig Venter, Ph.D., and FDA Commissioner Margaret Hamburg, M.D., talk about the importance of the Archon Genomics X PRIZE competition.]

Among participating centenarians is Dennis Morris, who turns 106 next month. Each week, the retired teacher writes a newsletter emailed to 46 friends and family members. Until losing muscle tone in his legs about a month ago, he maintained an exercise routine that combined walking with more vigorous activities like arm stretches, Morris’ daughter Nancy Luthy, 70, told GEN.

She says Morris still starts each day with two breakfasts: One of oatmeal, wheat germ, and prunes; the other, eggs (scrambled or over hard) and bacon or sausage.

“We are finding as we go to the doctor and he has tests that he might have a low number—one of his blood numbers might be low. And our question is, is that normal for someone 105? Most doctors do not have an answer,” Luthy said. “There’s not much data for 100-year-olds, much less 105-year-olds. He wanted to participate in the program because he wants more information about centenarians to be available.”

The major studies of centenarians may have succeeded over the years by taking a more positive tack than many studies of aging and longevity. Rather than require participants to rehash what they did wrong, they and their families are instead asked to recount what they did right, and how others can learn from them.

“We’ve gotten a lot of buy-in from our families and our study participants in being excited with us about the possibilities of figuring this out. It is work that makes us feel very good, too,” Winifred Rossi, deputy director of the Division of Geriatrics and Clinical Gerontology of NIH’s National Institute on Aging, told GEN.

Since 2006, NIH’s National Institute on Aging has sponsored LLFS to learn why some families have several members that live to be 90, or 100 or even older. Data has been collected by researchers at University of Southern Denmark and three U.S. schools: Columbia University; University of Pittsburgh; Boston University Medical Center. A fourth, Washington University School of Medicine, is LLFS’ data-management coordination center.

“It has completed all the health data collection, and the environment data collection, and the demographic data collection. It has collected all of the blood, the DNA samples from everyone in the study,” Rossi said. “Now we’re beginning to do the analysis on that, including genome-wide association, genotyping, as well as sequencing. And the hope is, to be able to put what we found from those massive amounts of genetic data together with the health and environment data, and try to find patterns, so that we can figure out what is it that we can say that represents exceptionally healthy aging and longevity.”

Unfortunately, LLFS has been hamstrung by budget cuts that have reduced available grant funds and the number of researchers who can track down and assess data. Rossi said LLFS researchers will apply soon to renew grant funding, set to end in August 2013. While Congress must contain spending, it should weigh carefully whether the short-term savings from cutting LLFS really outweighs its potential long-term benefits such as reduced healthcare costs.

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