Research programs embody the promise of anti-aging medicine.

USC Davis School of GerontologyDec 13 2010

Sometimes the value of research lies as much in exposing false remedies as in discovering true breakthroughs. Scientists at the country's first school of gerontology and in laboratories around the University of Southern California do both, mindful of their responsibility to a society focused on healthful aging.

To understand the promise and pitfalls of anti-aging therapies, start with the research and lifestyles of anti-aging scholars.

Valter Longo knows how to give yeast cells 10 lives, but neither he nor any other biologist knows for sure how to add even one year to the human lifespan. So Longo plays the Longevity Casino with a conservative strategy: exercise moderately, follow the Okinawa diet (whole grains, vegetables and fish) and leave the table a little hungry.

Christian Pike believes in a link between low hormone levels and Alzheimer's disease, and he has seen how middle-aged mice perk up when given testosterone. Yet he is leery enough of potential side effects that he advises his own parents not to take hormone supplements, and jokes that so far he has resisted the temptation to dip into his laboratory's testosterone stock.

Caleb Finch, a world authority on inflammation and aging, takes statins to control his cholesterol level, and also because the drugs appear to tame damaging inflammatory substances. He swims regularly but does not like to push his body too hard.

These experts' ambitious research programs embody the promise of anti-aging medicine. Their lifestyles reflect their modest personal approaches to longevity. Nowhere is the rift between theory and practice wider than in the pursuit of longer, healthier lives.

The 1990s were supposed to break open the promise of gene therapy. Tom Johnson of the University of Colorado startled the research world in 1990 by reporting that the mutation of a single gene could more than double the maximum lifespan of earthworms. Confirmed and extended by Cynthia Kenyon of UC San Francisco in 1993, the experiments showed that the mutated worms not only lived longer, but also looked younger and fitter.

Scientists then achieved lifespan extension of 30 to 50 percent in genetically engineered mice. By 2008, at the USC Davis School of Gerontology - the first such school in the country - Longo's laboratory had achieved a record tenfold lifespan extension in genetically engineered baker's yeast.

Genetically engineered humans are a different brew, for both ethical and technical reasons. In a 2010 review of lifespan extension in the journal Science, Longo noted the lack of mutation studies even on monkeys and other primates. If and when such studies are done, results will not arrive for decades due to the long lifespan of the animals. Ethical questions about gene therapy and genetic engineering in humans guarantee additional, possibly indefinite, delays.

The efficacy of longevity therapies marketed today will not be proven for at least a generation. Nature abhors a vacuum, and scammers are quick to spot an opportunity. The anti-aging industry is an obvious magnet for charlatans.

Yet in theory, the genetic study of longevity holds vast potential. If scientists can identify genetic mutations that prolong lifespan - and a few strong candidates have emerged from studies of centenarians around the world - drugs that mimic the action of those mutations might also mimic their life-prolonging effects.

For the past few years, a group led by Longo has been studying a few hundred Ecuadorians who appear immune to cancer. Members of this isolated mountain community share a mutation that makes them insensitive to human growth hormone - resulting in dwarfish stature but possibly lowering the risk of cancer, since the same genetic pathway has been linked to tumor growth.

Longo's group is trying to verify whether the Ecuadorian subjects are truly resistant to cancer and whether they live longer than other populations. A related group with a mutation inherited from only one parent holds special interest: Subjects in this group are of normal height, yet may still possess unusual cancer resistance. Results from the Ecuadorian study are not expected for several years.

At USC's Davis School and in laboratories around the university, biologists focus their energy on credible strategies for lifespan extension - while also collaborating with demographers, sociologists, social workers and psychologists in a broader discussion of aging - not as an avoidance of disease, but as a natural condition of life.

THE BULK OF LIFESPAN extension, to date, has come from improved public health: clean water, better hygiene, immunizations, safer childbirth. Modern medicine has lowered mortality from heart disease somewhat and lowered cancer rates very slightly since 1990 (cancer mortality had risen steadily up to that point). In 1996, Finch and colleague Malcolm Pike of the Keck School of Medicine of USC authored an influential paper suggesting that 120 years would be a feasible average human lifespan if caloric restriction worked as well in people as in mice. (So far only one human has lived past 120: Jeanne Calment of France, who died in 1997 at age 122.)

We are moving slowly toward a triple-digit lifespan. Life expectancy for a person born in the United States today is about 78 years - up from 71 years in 1970, and 60 years in 1930.

But the rising numbers mask deterioration. The age curve is starting to level off, or at least to rise more slowly. Medical technology keeps some people breathing who may not wish to keep living - not just the brain-damaged on ventilators, but older adults on pacemakers and other devices whose minds decline while their artificially supported bodies show stubborn stamina.

Even with technology prolonging lives of dubious quality, the United States lags in the race to 120. At a conference this spring hosted by USC's Davis School and the Office of the Vice Provost for Research Advancement, noted demographer Eileen Crimmins, a professor of gerontology at the school, showed that the United States ranks lower than many developed countries.

"It's hard to find any evidence that we're in good shape relative to anyplace else," says Crimmins, who holds the AARP Chair in Gerontology at USC and is director of a joint USC/UCLA center on biodemography.

Some attribute the poor U.S. showing to violent crime and infant mortality in the inner city - tragedies to be sure, but ones that would suggest a much better outlook for the middle class. However, Crimmins' data offer no such comfort. She compares life expectancy starting from age 50. Infant mortality has no influence on her numbers, and since most victims of crime are younger, violent death is a negligible factor.

Instead Crimmins blames past smoking, especially by women; a high incidence of heart disease and diabetes; high rates of physical disability, possibly related to obesity and sedentary lifestyles; and variation in disease and mortality by class, with well-educated Americans doing somewhat better.

"People who are poor and have low education live shorter and less healthy lives," she says, regardless of their race.

Crimmins' frequent collaborator, University Professor and neurobiologist Finch, described a future in which most people will lead less healthy lives than the wealthy few, due to rising health care costs and uneven environmental conditions.

"There are very powerful counter-longevity forces that are building," says Finch. "Future benefits of longevity may be limited to a very small privileged group of people."

Against that backdrop, how can the average person stay healthy longer?

LEAVING FOOD AND LOVING IT

Biologists agree that only one strategy has been shown to extend lifespan in a range of animals. As often happens, it is the least pleasant option in the spectrum of alleged anti-aging remedies, which includes such enticing elixirs as red wine (for resveratrol, a much-touted but unproven tonic), blueberries (for their anti-oxidant properties) and growth hormones (for their libido- and muscle-building capacity).

The strategy is caloric restriction - a euphemism for staying hungry. As early as the 1930s, scientists noticed that mice fed a low-calorie diet lived longer than their counterparts that were fed a normal diet. Scientists speculate that partial starvation drives organisms into a highly stress-resistant state, what Longo calls a "maintenance mode." He views caloric restriction - or CR - as a way to fool the body into holding out for better times. The strategy seems to act as a natural kind of genetic engineering, reducing the activity of key genes involved in growth and development but linked to cancer later in life.

A study in macaque monkeys is starting to yield results. Begun in 1989 at the University of Wisconsin by Richard Weindruch, who like Longo is a former graduate student of caloric-reduction pioneer Roy Walford of UCLA, the study shows that underfed monkeys develop far fewer age-related disorders such as cancer, diabetes and heart disease. Unfortunately, they also are more likely to die from unusual causes (caloric restriction has been linked to a weakened immune system).

Overall the calorie-restricted monkeys seem to live longer, but the difference so far is not statistically significant.

The case for CR developed complications this year with the release of a study by James Nelson, a former graduate student of Finch now at the University of Texas Health Science Center. Nelson compared 41 genetically engineered strains of mice and found that more strains lived shorter lives with caloric restriction than actually benefited. (Longo cautions that Nelson's mice had their caloric intake cut almost in half, making it likely that many simply starved.)

Four years earlier, Nelson's UT colleague Steven Austad had shown that caloric restriction does not work on wild mice, raising the possibility that the whole thing may be a laboratory effect.

In a paper published last year in Proceedings of the National Academy of Sciences, Mark Mattson of the National Institute on Aging questioned the value of studies based on lab mice. He noted that lab mouse populations are unnatural in several ways. For example, they are bred to reproduce very quickly and grow very fat with no limit on their food intake.

There had always been CR skeptics among longevity researchers, but until recently Mattson wasn't one of them. "He was one of the defenders of this idea that caloric restriction is universal," says Raj Sohal, a professor in the USC School of Pharmacy.

Sohal himself was an early believer and co-author, with Weindruch, of an influential Science paper on caloric restriction. Sohal has since qualified his enthusiasm, as in a widely publicized study with Michael Forster of the University of North Texas that compared a fat and a lean mouse strain and found that caloric restriction helped only the chubby mice.

Critics point to these studies as proof that results from lab mice do not apply to humans. But consider the following laboratory population:
• Three quarters of males and nearly two-thirds of females are overweight or obese.
• Specimens have access to cheap, energy-dense food around the clock.
• Abundant calories help the young develop and reach reproductive age faster than their counterparts in food-scarce environments.
• Opportunities for physical activity are limited.

THAT DESCRIBES Americans today, according to scores of studies, including the latest weight statistics from the Centers for Disease Control.

"Humans are behaving exactly like lab mice and rats," Sohal says, with evident disgust.

So maybe caloric restriction could work for today's couch potatoes. But even a caloric restriction enthusiast like Longo urges caution, pending the results of two clinical trials with some brave and very disciplined human volunteers.

"These guys are super skinny. I look skinny; imagine me minus 20 pounds," he says, pointing to his six-foot, 172-pound frame. "The point of these diets is to get you to weigh 25 percent less than normal.

"It's very extreme, too extreme," he says. And unproven.

Instead, Longo supports time-tested diets such as those followed by the long-lived people of Okinawa: meals rich in vegetables, whole grains and fish, complemented by physical activity and governed by the principle of hara hachi bu (eat only until 80 percent full). Or, closer to Longo's own ancestry, the Mediterranean diet of his Southern ltalian parents.

"Hamburgers? Even chicken was out of the question," Longo said. "They ate a lot of vegetables, not that much fruit actually, when they could get their hands on it some cheese - a little bit - but other than that, it was grains, whole grains a lot of the time, and that's it. And meat was just once a month.

"My father is 85 and he eats meat sometimes, but most of the time he eats a pretty good diet: green beans, some pasta, a lot of other vegetables thrown in there, carrots and leafy greens.

"Not surprisingly, now they (Southern Italians) are one of the longest lived in the world, together with the Japanese. Is it going to last? No, because the new Italians are eating like Americans."

Caloric restriction may leave its biggest mark in the cancer clinic. In March 2008, Longo surprised the medical community with a study showing that tumor-carrying mice forced to
fast before chemotherapy showed fewer side effects and tolerated higher doses than normally fed mice.

Longo theorized that short-term starvation drove healthy cells into a stress-resistance maintenance mode, but didn't slow the activity of cancer cells.

That would make all the difference in chemotherapy, which attacks the most rapidly dividing cells. In theory, Longo's group had found a way to protect healthy cells during treatment.

Because fasting can be dangerous, especially for weakened individuals, Longo urges cancer patients not to try it on their own. Clinical trials at USC Norris Cancer Hospital and at the Mayo Clinic in Rochester, Minn., are testing the safety of this approach in humans.

ELIXIR OF YOUTH

There is an elixir of youth, and its name is youth. All substitutes have failed the test.

It sounded too good to be true: You could enjoy red wine and longer life. Soon after its discovery in 2003, a grape ingredient called resveratrol made headlines in media from the British tabloids to The New York Times. In 2008, the group behind resveratrol, led by David Sinclair of Harvard Medical School, sold its small company to GlaxoSmithKline for $720 million - and no doubt celebrated with a fine glass of red.

Resveratrol and related compounds still might prove their value in ongoing clinical trials against adult-onset diabetes, inflammation and cardiovascular disease. But as the journal Nature reported this year, scientists see technical flaws in the experiments that made resveratrol famous. Further, a Pfizer-funded study concluded that resveratrol and related compounds were dubious drug candidates due to their many potential side effects.

Recently, two more studies came out. One, in the journal Cell, claimed that the gene allegedly activated by resveratrol - SIRT1 - slows Alzheimer's symptoms in mice engineered to over-express the gene.

A study in The Journal of Neuroscience, led by Valter Longo, found that while SIRT1 is important for learning and memory, over-expressing the gene does not improve cognition in mice.

"This is a very controversial topic since [proteins in the SIRT1 family] have been shown to be both good and bad," Longo notes. "In our previous studies [in mice and mammalian cells], for example, we showed that it was the absence of SIRT1 that protected neurons."

At the very least, the conflicting results suggest that taking a walk around the block may do more good than driving to Walgreens for resveratrol pills.

Widely prescribed for lowering cholesterol, statins also appear to reduce inflammation, which Finch and others have linked to aging and cell damage.

"The great question," says Finch, "is, 'What can we learn from existing anti-inflammatory drugs and diet manipulations that influence the inflammatory process that are going to be applicable to maintaining human health?' "

Statins may yet help scientists probe the connection between inflammation and aging. But whether statins themselves prolong life remains an open question.

"Everybody thinks statins do good things, and so nobody wants to rock the boat," Crimmins says. But when she and a group of geriatrics researchers from UCLA submitted an article to a leading journal showing that statins used in the treatment of cholesterol have no effect at all on survival in old people, the article was rejected.

"Honestly, I was shocked," she recalls. "The editors said, 'We're not interested in this paper because the use of statins is so ingrained in practice right now that it would upset things too much to say this kind of thing.'

"We don't know what the statins are doing," she adds. "But everybody thinks that statins in theory should be good for a lot of things, not just cholesterol; that they should lower your inflammatory burden; maybe they are good for your cognition."

If a food's marketing literature, and maybe even the food itself, is "loaded with powerful anti-oxidants," will it help you live longer? No one would love to say yes more than Kelvin Davies, a top authority on the damage caused by oxidative stress. Holder of the James E. Birren Chair in Gerontology with a joint appointment in molecular biology in USC College of Letters, Arts and Sciences, Davies coined the term "oxygen paradox" to describe the conundrum facing almost all life on earth. Animals need oxygen to breathe, but respiration produces free radicals - highly reactive and toxic oxygenated byproducts.

Davies also discovered two "mechanics" in the cell that break down proteins damaged by free radicals. For reasons unknown, the mechanics slow down with age, and eventually close up shop.

Davies' findings echo research on fruit flies by John Tower, a professor of computational and molecular biology in USC College who has a joint appointment in the USC Davis School. Tower's group showed that free radicals can serve as useful and necessary carriers of signals between cells. During youth and middle age, the cells' mechanics, such as those discovered by Davies, fix any damage done by free radicals.

But in the last third of life, say Davies and Tower, something goes wrong.

"Our ability to get rid of damaged proteins seems to be declining - are we making abnormal proteins at a greater rate, or are we failing to get rid of them?" Tower asks.

Scientists are no different than others in hoping for clear, simple solutions. For a long time, it seemed that aging boiled down to accumulated damage from oxidative stress. Now, Davies says that when he is "very honest" with himself, he sees a cloudy picture: one that involves some increase in oxidative stress and some decrease in the body's ability to remove and repair damage - with the two changes feeding on each other and causing an exponentially rapid mental and physical decline in old age.

Davies' colleague John Walsh, associate professor of gerontology, believes oxidative stress plays a leading role in the part of the body that he studies: the basal ganglia, a region of the brain involved in motor function and movement disorders such as Parkinson's disease.

Because the brain consumes more energy than any other organ, it contains more mitochondria - the energy factories of the cell. Mitochondria convert oxygen into useful energy and spit out free radicals as byproducts. The more mitochondria, the more free radicals.

In addition, biologists agree that mitochondria degrade through chance DNA mutations, leading to greater production of free radicals with age.

"The more of these mitochondria you have," Walsh says, the more prone you are to damage. "Two percent of the time, just because of the randomness of biology, you're going to be generating free radicals in normal mitochondria."

If this is true, why can't you just load up on anti-oxidant blueberries and be fine?

Maybe it is a question of timing and delivery, Walsh speculates.

Davies is skeptical. He doubts higher doses or better delivery would help. First, the body contains thousands of different free radicals, and vitamins C and E fail to take out some of the most common types.

On a chemical level, Davies sees a point of diminishing returns where ingesting more anti-oxidant molecules will bring little benefit. Whether a river is lined with 100 or 200 fishermen during salmon season, some fish will always get away.

In addition, vitamin A has been shown to raise the risk of lung cancer and vitamin C seems to protect cancer cells.

So load up on powerful anti-oxidants if you wish, but realize that beyond a common-sense dose, they offer scarce protection and may carry unexpected risks.

ELIXIR OF YOUTHFULNESS?

Estrogen and testosterone supplements may not help people live longer. They might even kill you sooner. But they could make the ride to oblivion more enjoyable.

In 1994, when Finch was directing USC's Alzheimer Disease Research Center (now headed by Keck School neurologist Helena Chang Chui) and musing aloud about a possible link between dementia and estrogen, his then-colleague Victor Henderson gathered surprising data from women living in the Leisure World retirement community in Laguna Woods, Calif.

"Among women who had used hormone therapy, the dementia prevalence was about 50 percent lower," Finch recalls. "It was a very strong correlation. That is one of the key pieces of evidence in the chain that has led to this really quite large field: studying hormones in relation to Alzheimer's."

Correlation does not equal causation, but the link made sense to many biologists. Estrogen is critically involved in the production of energy, and the brain is the most energy-intensive organ in the body. It seemed plausible that a lack of estrogen might contribute to neural deterioration. More than two-thirds of Alzheimer's disease victims are women.

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.

ELIXIR OF AGE

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."