BAKER'S YEAST AND GENETICS

The oldest known person, Jeanne Calment of France, died in 1997 at the age of 122. Researchers compared her medical history with other people who’d lived to be more than 115 years old. They found the small group shared a few characteristics: most were female, they rarely or never smoked, and they had never been obese. But scientists still have a lot to learn about these supercentenarians.

S. Michal Jazwinski, the John W. Deming, MD, Regents Chair in Aging and professor of medicine and biochemistry at Tulane School of Medicine, has studied the aging process for more than 30 years. He also directs the Tulane Center for Aging, a collaboration of Tulane experts in everything from endocrinology to economics. Jazwinski is also the president of the Gerontological Society of America (GSA). GSA is the nation’s oldest and largest interdisciplinary organization devoted to research, education and practice in the field of aging.

Jazwinski’s own research centers around the genetics of aging and the molecular and cell biology of getting older. He pioneered using baker’s yeast, the same kind used to make bread, as a model for his own research.

The yeast ages much in the same way human stem cells do, which allows researchers to easily identify genes and focus on the molecular processes that are involved in aging. This work points to the critical role that mitochondria, the energy factories of the cell, play in aging. Cells compensate for the dysfunction of mitochondria that accumulates during aging, up to a point. In addition, less functional mitochondria are segregated asymmetrically between daughter cells during cell division, allowing one of them to remain young. The same process occurs in stem cells with older, less functional mitochondria. When this asymmetric segregation is disrupted, the stem cells lose their stemness properties, leading to stem cell exhaustion and eventual loss of tissue function.

Jazwinski’s lab is also studying human aging. He is part of the Georgia Centenarian Study, an ongoing study started in 1988, which in its current phase examines factors that contribute to retention of cognitive and physical function past the age of 100.

Jazwinski also directs the Louisiana Healthy Aging Study, which brings together researchers from Tulane, Louisiana State University Health Science Center in New Orleans, Louisiana State University in Baton Rouge, Pennington Biomedical Research Center in Baton Rouge and the University of Alabama at Birmingham. The researchers have identified an interaction of three genes that promotes longevity and healthy aging.

“One of the things we’ve been able to do is establish a measure of biological age,” Jazwinski said. Calendar age, or how old a person is according to their birthdate, isn’t a good predictor of how long they’ll live because of differences in genes, the environment, lifestyle and more.

“As individuals age, they begin to become more and more different from each other; the older they are chronologically, the more they differ from each other in terms of their functional ability and other manifestations of aging, even how they look,” he said. “Knowing someone’s biological age allows you to tailor therapies and interventions that promote healthy aging, as well as treat various disease and trauma based on the biological age of the person, bringing us into the realm of precision medicine.”

Strikingly, increased biological age in older people takes its toll in an increase in the energy required for maintenance of basic body functions. The way this plays out differs between men and women, but in both, different aspects of mitochondrial function appear to be involved.

TULANE CENTER FOR AGING

Tulane established the Center for Aging in 2007 to enhance the quality of life of an aging population through research, education and innovative approaches to healthcare and community planning and design. Led by Jazwinski, the center brings together multidisciplinary resources at both the uptown and downtown campuses along with the Tulane National Primate Research Center. It also offers an interdisciplinary PhD program in aging studies.

The center’s research focuses on cognitive aging, neurodegenerative disorders and dementia, including Alzheimer’s disease. Among the initiatives is a broad attack on the age-related aspects of cancer and cardiovascular disease, as well as musculoskeletal aging including osteoarthritis and osteoporosis.

“The population is living longer,” said Jazwinski. “In a few years, there are going to be some 80 million retired baby boomers and they expect to be high functioning. Those who aren’t will need help and this is going to pose a certain economic burden on society.

“What I’d personally like to do is to add life to years rather than years to life.”

COBRE GRANT

Five junior investigators at the Center for Aging are working on projects funded by a federal Centers of Biomedical Research Excellence (COBRE) grant in “Aging and Regenerative Medicine.” Currently in Phase II of the 10-year grant, the projects target central nervous system and vascular aging, immune system aging, degenerative disorders of the brain and musculoskeletal system, as well as the larger issues surrounding cell senescence and chronic inflammation.

SOFT TISSUES

Kristin Miller, an assistant professor of biomedical engineering in the School of Science and Engineering, studies how soft tissues grow and remodel.

“I approach things from a mechanical engineering perspective of looking at what enables biological tissues to perform their necessary function within your body,” she said.

Miller’s research focuses on tendons. She identified a collagen that’s key to how a tendon works and recovers from injury and developed math models to describe changes that happen to the collagen that might be responsible for the loss of tendon function that comes with age.

“I think one of the coolest things about having the COBRE grant is it brings together people from all different backgrounds and expertise,” Miller said. “My expertise is in math models that link proteins to functions but there are people on the grant whose expertise is more of understanding some of the specific aspects of the biology of collagen and the molecules that control its production and removal, so it’s important for me to interact and learn from them.”

STRONG BONES

Mimi Sammarco, an assistant professor of surgery at Tulane School of Medicine, is studying bone and soft tissue regeneration under the COBRE grant.

“The older you are, your bone turnover and bone density become lower, so it’s much harder to do things like heal fractures well or have strong bones,” Sammarco said.

Using a mouse model, Sammarco has learned the soft tissue surrounding the bone changes with age. She’s now trying to determine if that environment around the bone is linked to regeneration.

Sammarco believes her research can address a large population of people.

“It’s not just about living longer, it’s about aging well,” she said. “Having strong bones is an integral part of mobility.”

ALZHEIMER'S DISEASE

Neuroscientist Jay Rappaport became director and chief academic officer of the Tulane National Primate Research Center (TNPRC) in June. He wants to expand the portfolio of the TNPRC by doing more research on diseases like Alzheimer’s. An estimated 5.7 million Americans have the irreversible brain disease, and the Centers for Disease Control predicts that number will climb to 14 million by 2060.

“This is going to put an enormous strain on the healthcare system, on the economy and on families,” said Rappaport.

“If you look at the drugs that have been developed for Alzheimer’s disease, their track record: between 2002 and 2012, there were 244 drugs tested in clinical trials. Only one was approved and it was only for symptoms; it didn’t stop the progression of the disease. That’s a 99.6 percent failure rate, which is unheard of.”

The majority of these lead compounds have come from mouse studies. Rappaport said the National Institutes of Health have recently been ramping up funding for research into Alzheimer’s. It will be important for the understanding of the disease and the development of effective therapies to have models of Alzheimer’s disease that better replicate the human disease.

The TNPRC is adding close to 50 African green monkeys, 10 of which are more than 15 years old, to its colony of rhesus macaques. The center already has a number of aging macaques, and Rappaport said there is some evidence they have some of the features of Alzheimer’s disease as they age. It takes more than 20 years for those signs to appear though, while African green monkeys show signs of Alzheimer’s disease somewhat earlier.

The center recently received a PET/CT Scanner from the Bill & Melinda Gates Foundation for its work on developing tuberculosis vaccines. The scanner provides noninvasive imaging of live animals and is specifically designed for monkeys. While the primary use will be for Tulane’s tuberculosis research with the Gates Foundation, Rappaport said it can also be used to study aging and will enhance the center’s HIV vaccine studies.

Rappaport’s research, and that of other investigators within the Primate Center, focuses on HIV infection, HIV/AIDS–related disorders of the nervous system and the development of therapies for treating AIDS. His recent studies show the simian version of HIV accelerated inflammation and markers of aging in infected monkeys, but Rappaport also is testing a nutritional supplement that appears to reduce inflammation and may slow the pace of biological aging.

LONG AND USEFUL LIVES

Underpinning the research on longevity at Tulane is a recognition that having a productive, satisfying and mobile life in one’s later years is as important as adding years to one’s life. As the population ages, Tulane is prepared to play a leading role in finding ways to make that happen.

(Main photo: Emma Louise Brandt Elston of Buras, Louisiana, is 16 years old in 1925 (right). The photo (left) was taken on her 100th birthday, Jan. 26, 2009. She died one month later. By all accounts, she lived a happy, productive life.)