Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Unknown genes are postulated to promote slower and healthier aging in some people.

Elizabeth Kirwan was trained for lab work so long ago, she recalls, that she and colleagues counted blood cells using a hemocytometer, and carried out all required chemistry manually.

Kirwan, who turned 100 on May 8—she shares a birthday with Paramount Pictures—worked in the labs of several Los Angeles private hospitals before leaving her career behind to raise her family. These days, she stays busy by playing bridge, attending balance classes, and participating in some of the activities available at her San Diego senior community.

“I’m beginning to feel a little bit older. I don’t have the power and the pep I used to have. But considering how old I am, I feel well,” she told GEN.

Discovering how Kirwan and other centenarians have stayed healthy is the goal of the Archon Genomics X PRIZE presented by Express Scripts. On October 31, 2013, the nonprofit X PRIZE Foundation will award $10 million to the first investigator team that most rapidly, accurately, and economically sequences 100 whole human genomes from centenarians living in and outside the U.S.—“100 Over 100,” in X PRIZE parlance. Teams will have 30 days to sequence 100 whole human genomes of vital centenarians, with no more than 1 error per million bases (99.9999% accuracy) and a cost of $1,000 or less per genome.

“I think this is certainly going to be a wonderful thing for the future of medicine and the future of mankind,” Kirwan said. “It doesn’t hurt me to give my DNA. I’m happy to do it. It’s a wonderful thing to leave as a legacy.”

[For more on the Archon Genomics X PRIZE and for a brief interview with Elizabeth Kirwan, watch the video here.] 

The competition should add much to the knowledge emerging over the past two decades about how people can live to 100 or more. Much of that knowledge has been generated by three multiyear research efforts:

  • The New England Centenarian Study (NECS) is the world’s largest study of centenarians—about 1,600 of whom are enrolled—and their families. NECS is led by Thomas Perls, M.D., MPH.
  • The Longevity Genes Project (LGP) at Albert Einstein College of Medicine of Yeshiva University has studied more than 550 Ashkenazi Jews ages 95 and up to identify genes connected with longer life since 1998.
  • The Long Life Family Study (LLFS) united researchers from the U.S. and Denmark in collecting data from nearly 5,000 people belonging to about 850 families whose members have enjoyed exceptional longevity.

NIH’s National Institute of Aging (NIA) sponsors the LLFS, and is among funders of both the NECS and LGP studies.

Fountain of Health

“People are always sort-of looking for the fountain of youth. And what we’re looking for is the fountain of health,” Winifred Rossi, deputy director of NIA’s Division of Geriatrics and Clinical Gerontology, told GEN.

The major studies have found that while environment plays a larger role than genes in healthy aging—estimates range from 70%−30% (NECS) to 80%−20% (LGP)—the role of genetics seems to grow with age, especially past 100.

Centenarians are indeed rare—one of every 5,000 U.S. citizens, according to the 2010 U.S. Census, while one in 20,000 people are 105 or older.

The older the centenarians, the greater the progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity, according to a study based on NECS data and published April in the Journal of Gerontology.

The findings were consistent with the 1980 hypothesis of James F. Fries, M.D., professor emeritus at Stanford University School of Medicine, who posited that, as the practical limit of human life span is approached as with “supercentenarians” aged 110 and older, morbidity is compressed toward the end of their lives, resulting in a shorter period of illness.

“I think all of that compression of morbidity and disability speaks to some genetic advantages that help these individuals age more slowly, and markedly delay and in some cases escape certain age-related diseases, like Alzheimer’s,” Dr. Perls told GEN.

Those advantages, he added, may be affected by environment: “There could be certain exposures to certain environmental factors, or lack of exposure certainly—something like smoking. So I would not rule out the possibility of diet in some individuals playing a role. What that specific diet might be, we don’t know yet.”

That’s an area warranting at least as much further study as the genetics of aging to 100, where the major studies have proven most helpful.

“To be a centenarian, we believe that you need special genes­—that if you don’t have them, you can get maybe past 80, if you’re lucky maybe past 90, but not more than that,” Nir Barzilai, M.D., LGP’s lead investigator, explained.

He added, however, that genetics alone doesn’t fully explain why some people live past the century mark.

“It’s a total interaction. You cannot separate them. If you eat sugar, it will unfold the protein and increase its expression in the tissue, so that environment works directly on expression of genes. That’s an interaction. It’s not that they contribute equally,” said Dr. Barzilai, who is also the Ingeborg and Ira Leon Rennert Chair of Aging Research and director of the Institute for Aging Research at Einstein.

“If you look at exceptional longevity in families, it’s much more than 20% genetics. It’s 50% to 80%. One of the interesting things in our centenarians is that they mostly have a family history of longevity.”

That suggests the presence of genes not yet known that promote slower and healthier aging in some people.

“What that tells us is that there’s some small subset of the population that effectively won the genetic lottery. They’ve got the right genes,” Brian K. Kennedy, Ph.D., CEO and president of the Buck Institute for Research on Aging, told GEN. “Understanding what’s going on with these centenarians is critical. It’s a longer-term perspective. It’s not going to yield a treatment next year, but you’ve got to start.”

Extending Survival

One small but potentially significant step in that direction, he said, was the publication in July of a Buck Institute study finding that the immunosuppressant Rapamycin improved function and extended survival as much as 60% in mice suffering from a genetic mutation leading to dilated cardiomyopathy (DCM) and rare muscular dystrophies in humans.

The study initially focused on Rapamycin in a mouse model of Hutchinson-Gilford Progeria Syndrome, a premature aging disorder that, like DCM, is also based on a mutation in the lamin-A protein produced by the LMNA gene. Instead, researchers found to their surprise that rapamycin is beneficial for DCM instead.

“To me, the importance of that study is, at a minimum, it is a proof-of-principle that, if you can find one drug that [can show positive results], you can probably find 10. And the more of those you start to find, the more you increase your chances that one of them will be right. I think we’ll get there. I’m encouraged,” Dr. Kennedy said.

In overall aging, genetics may define human susceptibility to disease or longevity, yet its potential works not in a vacuum, but through interaction with the environment, Jose M. Ordovas, Ph.D., senior scientist and director of the Nutrition and Genomics Laboratory at Tufts University’s Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, told GEN.

While genetics has seen the greatest progress in information, if not translation, more progress can be expected due to high-throughput sequencing, Dr. Ordovas said: “We need much better capacity to properly and accurately capture the environment (i.e., nutritional information, environmental exposures and so on).”

He added, “Healthy aging may begin even before conception with the parents’ behavior. After that, the fetal environment may set the stage for the rest of our lives through epigenetic mechanisms driven by maternal nutrition, stress, environment, and so on. As we move through our life path we may have to change more to achieve less in terms of prevention and therapy of age-related diseases. However, it is never too late to do something for the quality-of-life in the elderly years.”

By the time people reach their 100th birthday, however, they reap the benefits of genes protecting them from diseases afflicting younger seniors, such as Alzheimer’s. What all those genes are, and how they work, remains unknown. Yet that protection explains why centenarian men are often healthier than 100+-year-old women, even though more women than men are 100 years old.

Secrets to a Healthy 100

Whether you have good genes or bad, how you behave is also a factor to consider when aiming for a long, healthy life. Florida Hospital recently came up with eight “Secrets to a Healthy 100” years or more as part of its Health 100 initiative to educate and motivate people to adopt healthy lifestyle changes:

  • Choice: Make healthy choices; accept responsibility for health and longevity.
  • Rest: Get a good night’s sleep, take time to relax during the day, and just “be” one day a week.
  • Environment: Maintain a healthy personal environment.
  • Activity: Stay active both physically and mentally.
  • Trust: Act on your faith; develop spiritual partnerships.
  • Interpersonal relationships: Stay in touch with friends and family.
  • Outlook: Keep a positive perspective on life.
  • Nutrition: Eat healthy; even small improvements make a big difference.

[Source: Florida Hospital Healthy 100]

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