NYC Healthcare News

Research programs embody the promise of anti-aging medicine.

January 09, 2016

In a long-running study in Baltimore, Alzheimer's disease in men also has been linked to low hormone levels. The latest data suggest that men in the study who developed Alzheimer's had low testosterone even when healthy.

"Low testosterone seems to occur prior to the development of dementia," says USC Davis School gerontologist Christian Pike, whose team studies sex hormones and the development of Alzheimer's disease. "In that case it's likely one of many contributing factors."

When given to neutered rats with low libido, testosterone makes them "all better," Pike says. Disgraced cyclist Floyd Landis demonstrated testosterone's power in an amazing solo ride over a mountain stage of the 2006 Tour de France. The amazement was not limited to fans. Tour officials and medical experts were amazed at the testosterone levels in the two positive urine samples from Landis that day - levels so high they could not have been reached naturally.

So why not prescribe testosterone for all middle-aged men? Pike admits that more men are getting prescriptions for the hormone and, so far, conclusive evidence of major health risks is lacking. Every time Pike talks about his research at a social event, some older man half-jokingly volunteers for a trial.

"The most reproducible effects are decreased fat, increased muscle," Pike says. "You're going to be leaner, trimmer, feel better."

But he does not plan to use the hormone, and he has advised his father not to take it either.

"It's one of those hot anti-aging drugs," he says. "But any time something like that comes along, you have to be nervous because you don't know what all of its effects are.

"You wait. There's going to be some downsides."

Not a day after this was written, a study linked testosterone supplements to an increased risk of heart attacks.

Testosterone therapy may wind up driving off the same cliff as estrogen replacement. Millions of women stopped taking estrogen in 2004 after a massive trial showed little benefit and an increased risk of stroke. A trial of estrogen in combination with progestin had been stopped earlier, in 2002, due to an increased risk of breast cancer, coronary heart disease, stroke and pulmonary embolism. (The studies also found some benefits, notably a decreased risk of bone fractures and colorectal cancer.)

The news was a major setback for estrogen therapy researchers. USC's Roberta Brinton considers herself an exception. Professionally, she believes her research shows that estrogen has a "healthy cell bias," improving brain function when the organ is healthy but making matters worse when neurons degenerate.

Personally, Brinton continues taking estrogen to counter symptoms of menopause and, she believes, to lower her risk of Alzheimer's disease.

Brinton, a professor in the USC School of Pharmacy with joint appointments in engineering and medicine, was featured in a New York Times Magazine feature that explored the "timing hypothesis": that estrogen may be helpful against Alzheimer's if started early, during or soon after menopause.

Other scientists caution that estrogen therapy carries a risk of serious health problems whether started early or late. It is clear that the loss of estrogen during menopause imposes a tremendous burden on some women.

"We're on the clock," Brinton says of her team's battle to vindicate estrogen therapy just as a massive wave of Baby Boomers approaches a point where the mind will fail before the body.

"Women can now expect to live a third of their lifetime in the post-menopausal state. We now know this has profound implications for the brain and particularly for its ability to convert glucose into the energy the brain needs to function. I liken it to that 30 percent drop in people's stock portfolio, which many have experienced during this recession. It didn't kill you, but it really hurt."

Some women make up the loss, or at least adjust fairly well. Others need help to recover. Others, for poorly understood reasons that may include estrogen depletion, begin the slide into dementia.

In a long-term clinical trial at the Keck School of Medicine, faculty members Wendy Mack and Howard Hodis are testing different combinations of estrogen and progesterone in the hope of finding a safe hormone replacement therapy.

Finch, Brinton and Pike are starting joint work on a research grant to study the link between hormone therapy and inflammation. Estrogen deficits seem to impair the body's ability to fight inflammation, Finch says.

Taxpayers should be rooting for Brinton. If lifespan keeps increasing and no one figures out how to slow Alzheimer's, society will face a staggering financial and emotional burden.

Health care economist Dana Goldman, director of USC's new Leonard D. Schaeffer Center for Health Policy and Economics, a collaboration between the USC School of Pharmacy and the School of Policy, Planning, and Development, is an optimist on lifespan and a pessimist on Alzheimer's.

"Cancer became a social epidemic in this country because we finally lived longer to age into cancer," he says. "[Alzheimer's] is the next social epidemic. Our bodies will survive, but now we have to figure out how to keep our minds in shape."

As hard as cancer can be on a patient's family, Alzheimer's represents a lower circle of hell.

"Cognitive decline from Alzheimer's affects everybody in a very fundamental way," Goldman says. "When you can't recognize your family members but they have to take care of you, that imposes an incredible amount of wear and tear on the other family members. Cognitive decline is infectious in a different way than infectious disease."

It is hard enough to look after normally aging relatives. William Vega is learning this firsthand as he tries to balance his responsibilities as a parent, as director of the Edward R. Roybal Institute on Aging in the USC School of Social Work and as dutiful son to aging in-laws who require expensive home care.

Vega's mission as institute director is to help people age in their own homes and their own communities. It is easier said than done. (Jon Pynoos of the USC Davis School has been working on this issue for more than 30 years, both with home design and fall-prevention strategies.)

Consider an octogenarian couple. An 84-year-old woman is going to have a real problem lifting her husband off the floor when he falls, Vega says.

As chair of the prestigious Institute of Medicine's Health Care Disparities Roundtable, Vega has spent years studying the social and financial stress on families who lack access to health care. They experience a vicious cycle where financial stress leads to emotional and health stress, which leads to more financial stress, and so on.

"We already know that low-income people age faster than upper-income people," he says. The difference is already apparent by age 25: more than a six-year gap in expected lifespan, according to Vega.

And today's children are more likely to lack the economic opportunities enjoyed by their parents, Vega believes.

While awaiting a breakthrough in Alzheimer's research, worried individuals should know that DNA is not destiny. Decades-long studies on twins by USC psychologist Margaret Gatz and others have found big societal influences on cognitive health and aging. Studies have shown the protective value of love, friendships and social networks, not just against Alzheimer's but to slow aging overall.

In a paper published this year in the freely accessible PLoS Medicine journal, researchers from Brigham Young University analyzed dozens of studies on longevity and social ties, and concluded that having strong networks of friends, family and colleagues improves one's odds of survival by as much as 50 percent.

The long-running Australian Longitudinal Study of Aging found similar benefits for participants with strong friendships.

It is a message you will never hear from the pharmaceutical lobby: A supplement is no substitute for a friend.


Aside from the stereotypical (and not entirely true) decline in function, libido, earning power and mental sharpness, aging is just terrific. That is the conclusion of several studies that consistently show an increase in happiness as people enter their 60s. This "positivity effect" intrigues gerontologist Mara Mather, a young associate professor in the USC Davis School.

Mather has been conducting brain-imaging studies to try to understand the phenomenon. First she wondered if fear-related areas of the brain simply shrank as the brain aged. But that does not seem to be the case, Mather says.

Her initial results suggest that older adults redirect their brains to positive thoughts without even realizing it.

"They tend to be more likely than younger adults to ignore negative information," she says. "A larger percentage of what they remember tends to be positive."

To test her conjecture that the positivity effect stems from willful effort, Mather tracked the time older adults spent looking at a series of positive and negative images. If allowed to concentrate, the study volunteers looked mainly at positive images. But if Mather added a distracting sound or visual cue to the test, older subjects were no more positive than young adults.

"If they had a cognitive load, they were unable to focus more on the positive things," Mather says.

Whether consciously or not, USC Davis School dean Gerald Davison finds it easy to focus on the positive things.

Professionally, he heads a resurgent school in a growth industry. Programs such as USC's Los Angeles Caregiver Resource Center and Tingstad Older Adult Counseling Center serve the entire region. For a school in what is still a niche field, student enrollment is a healthy 50 to 60 undergraduates, 100 professional master's students and around 25 Ph.D.s, and enrollments have been increasing over the past few years. The school just added two junior faculty: molecular biologist Sean Curran, a UCLA Ph.D. fresh from a post-doctoral position at Harvard Medical School and Massachusetts General Hospital; and psychologist Cleopatra Abdou, also a UCLA Ph.D. and, more recently, a Robert Wood Johnson Foundation scholar studying nonmaterial factors that influence happiness.

Personally, Davison is having the time of his life.

"Your priorities change as you get older, and there are things that you can no longer do as much, but they're not as important as they used to be," he says.

"Younger people have looked at older people and said, 'My God, you don't taste as much, you don't see as well, you don't get as much sex, your friends are dying ... who wouldn't be depressed?'

"That's the limited perspective of the younger person. What they're really saying is, 'Given my 45-year-old self, I look at those losses with horror, I say, oh God, those poor people.'

"And apparently that's not the case for most older people, the ones who have a reasonable amount of health. And these days there are more and more of them."

Source: USC Davis School of Gerontology