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Discovering the secrets of how age-related genes work

Discovering the secrets of how age-related genes work

Tuesday, June 23, 2015

There’s no question. Getting older means getting sicker. Conditions can be relatively minor and manageable – high blood pressure – or severe and complicated – dementia. It’s clear, though. A person who lives long enough will develop some type of ailment.

But, what if science could put a stopper in aging or at least put the brakes on a little? A group of researchers in the Social Science Research Institute (SSRI) at Duke University is working on doing just that, asking whether there’s a link between genetics and the likelihood a disease will strike an individual in the future.

“People have started looking at the genetics of aging, health, and longevity and the key idea that people are now spending a huge amount of money on disease,” said Anatoliy Yashin, scientific director of Duke’s Center for Population Health and Aging (CPHA). “But, if the diseases of aging are related somehow, why not focus on aging and postponing or slowing it down?”

If science reaches that goal, he said, it could change how healthcare systems approach aging and the associated chronic and acute conditions.

“Individuals who have some kind of frailty or vulnerability to disease die first,” he said. “This predisposition could be genetic, and if there are genetic differences, they should be taken into account when we consider the population composition is changing.”

Ongoing Research

Fundamentally, Yashin’s group wants to discover the secrets not only of how age-related genes work, but also of how they work together to cause sickness. Deciphering the details of those relationships could significantly impact health, lifespan, and tailored treatments.

“What we’re doing is related to personalized medicine. When we understand this well, we will contribute a lot to prevention,” Yashin said. “What you treat as a risk factor isn’t absolutely a risk factor. You must remember to consider genetic factors and the environment to understand how genes act at a specific age.”

Ultimately, he said, the team hopes to unearth two gene types that directly impact life span. The first will influence the age of disease onset, and the second will likely affect how long an individual lives after developing a condition.

To reach these goals, his team, including senior research scientists Svetlana Oukraintseva, Ph.D., and Alexander Kulminski, Ph.D., as well as senior research fellow Konstantin Arbeev, Ph.D., and research professor Eric Stallard, Ph.D., are tackling the science behind the genetics of aging through a three-pronged research effort: the genetic effects on life span, the genetic effects of aging, and how genes’ impacts changes over time.

Conventional wisdom points to multiple co-morbidities as a driving factor behind the speed of aging progression. But, according to the team’s research, the true nature of risk factors is more nuanced.

“It turns out when we talk about genetics and longevity factors of disease and life span, everything depends on the situation,” Yashin said. “Risk factors could change with age. The genetic risk could be present for a 70-year-old but be neutral for an 80-year-old.”

Clearly, he said, something changes within the human body as it ages, and understanding what and how it happens could unlock the mysteries surrounding why some individuals are long-lived.

But, even the slower aging among centenarians doesn’t guarantee a lower risk for disease, Oukraintseva said. Responses to stress will increase, and any recovery will be slower or incomplete. Instead, their longitudinal research revealed how gene functions morph and present themselves differently over time.

For example, she said, traditional research methods show older adults have a higher body mass index (BMI) than younger people. But without BMI data from longer periods – often decades – researchers can’t capture an accurate picture of aging and genetic effects. Collecting long-term data, she said, highlights exactly how genes influence bodily changes and how they relate to health and life span, directly or indirectly.

Additionally, third project results show genetic functions and mutations are not absolute – they shift and change throughout a person’s lifetime. This work strikes close to the heart of peoples’ desires for long lives – but only if they’re healthy. It’s possible, Kulminski said, for a gene to be harmful during middle age but have a protective benefit in older age.

“Our research shows genes – either good or bad – don’t create an unchangeable fate. They can work differently in different periods of human life,” he said. “This shows the effect on disease or survival and life span in only associated with specific age ranges. Genes can change their effect.”

For example, current investigations show a mutation of a single allele on a single gene can impact how the human body metabolizes lipids differently over decades. Knowing this, he said, could help doctors tailor how they treat high cholesterol in patients with this genetic alteration.

But older adults rarely have only one chronic or acute condition, making examining the associated genes necessary to learn whether – and how – they’re interrelated. Evidence exists, Oukraintseva said, that multiple gene mutations act differently together than they would individually, and analyzing these relationships could reveal how genes swing the pendulum between harmful and helpful.

The SSRI Difference

Having a team with such varied expertise is critical to successful research, Yashin said, but much of the work wouldn’t occur without extensive support from SSRI.

“[Nechyba] understands the importance of what we’re doing, and we’re very pleased with this,” he said. “SSRI is developing a more secure computer network, and we’ll probably be the first group to test its applicability for analyzing complicated problems and models that have millions of bits of genetic data.”

In addition to providing access to high-level, secure data, SSRI regularly brings this team together with other faculty to discuss challenges and to create synergistic efforts that could benefit the institution overall.

“The real value for Duke is in their mission statement of being excellent in everything they do,” Oukraintseva said. “They’re commitment to and support of us is reaffirmation they view our research as world class – among the best it can be at this time.”


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