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FINCH'S CAREER PARALLELS the explosion of interest in the science of aging. As the post-World War II baby boom generation slips from mid-life to retirement, aging has become a hot topic for scientists, the public and the health industry. Everyone wants to live longer, and live better.
Research has swept away some misconceptions. Until recently, for example, brain aging – everything from the annoying inconveniences of age-related memory loss to more serious conditions like Alzheimer’s and dementia – was equated with neuron failure. “I think historically the subject was thought to be very simple: that brain neurons were lost from birth onwards,” Finch says. “Now it is really clear that if you don't have a specific disease that causes loss of nerve cells, then most, if not all, of your neurons remain healthy until you die. That's a big change, and it has only come about in the last 10 years.”
At the same time, the human life span has increased steadily in the past century, and Finch believes we haven't yet reached the upper limit. But after 40 years of studying aging in humans and animals, he realizes there's no shortcut or magic potion.
“You can only go so far with extrapolating from lab animals to complex human biology. Maybe in 100 years we can do something more intelligent,” he says, but for now Finch recommends: “Keep your blood pressure down, don't get overweight, keep your blood sugar lower. And exercise! That's the best you can do.”
While reducing risk factors can prolong life, there's still no escaping certain diseases of aging. Cancer, heart disease and strokes can affect anyone, regardless of how much broccoli and exercise they get. One of the most debilitating and still least-understood diseases is Alzheimer’s disease, or AD – a degenerative brain disorder that afflicts 4 million and kills 100,000 Americans a year. The disease causes a person to forget recent events or familiar tasks; eventually it leads to confusion, changes in behavior and problems in communication. Most people suffering from Alzheimer’s become unable to take care of themselves.
In order to halt the disease, scientists like Finch first must understand how it is regulated, how it advances and what kind of cellular or molecular events – controlled by a combination of genetic and environmental factors – are responsible. In his third-floor research lab in the Andrus Gerontology Center, Finch and his team of postdoctoral fellows, graduate students and select undergraduates are pursuing several lines of investigation.
Over the years, the team has found that the female hormone estrogen protects brain cells from Alzheimer’s disease. Women develop AD at a higher rate than men of the same age, probably because of the postmenopausal drop in estrogen. Older males convert their male hormone testosterone into estrogen, which fights oxidation and inflammation of brain cells. Researchers are still trying to understand how men and women differ in the production of estrogen, and whether estrogen-replacement therapy in menopause protects against Alzheimer’s.
In April 2001, Finch’s team reported a crucial finding redefining the basic cause of dementia in the early stages of Alzheimer’s. Previous research had shown that plaque deposits (telltale microscopic lesions found in the brains of Alzheimer’s patients) surround and choke nerve cells in the brain and block production of an important chemical messenger. For two decades, Alzheimer’s research has focused on how these plaques form in the presence of a molecule called amyloid beta. Finch and his collaborators at Northwestern University still lay the blame on amyloid beta, but they describe a new, never-before suspected form of amyloid beta – called ADDLs – whose toxicological profile fits the symptoms of Alzheimer’s disease like a glove. Unlike the plaque-forming amyloid, ADDLs are soluble, which means they can diffuse everywhere in the brain. Previously researchers couldn't explain why some brain areas degenerate quickly with Alzheimer’s while neighboring areas remained intact. Amyloid beta plaques are confined to the locations where they first form – locations that correspond poorly with the brain areas that wither as AD progresses. ADDLs, on the other hand, affect exactly and exclusively the same clusters of brain cell that atrophy in AD patients.
To treat Alzheimer’s, Finch hypothesizes, one would need to block or disable ADDLs molecules rather than just attack the formation of plaques.
“It's the absolute opposite of where the research in this field has thrust itself,” he says. “It's as if everyone was looking at the spaghetti as the cause of Alzheimer’s when it's really in the marinara sauce.”
Speaking of pasta, Finch has also found that eating less may help in the fight against Alzheimer’s. As far back as the 1970s, Finch’s experiments with mice showed that those on restricted diets had lower rates of brain-aging diseases like Alzheimer’s. In research funded by the American Alzheimer’s Association, Finch’s lab is now looking at how reducing calories cuts down inflammatory cells in the brain and prevents other cells from aging. “I think one possibility is that [a low-calorie diet] lowers blood glucose levels,” he says. “Blood glucose is very reactive as a chemical and can cause damage to proteins.” People with diabetes (a condition producing elevated blood sugar) typically show more signs of brain aging than non-diabetic individuals, Finch points out.
“We've now shown that these inflammatory processes of aging, that are part of Alzheimer’s, are also slowed by cutting food intake,” Finch says. “It has ramifications for alternate approaches to treating Alzheimer’s.”

IN THE USC ALZHEIMER'S Disease Research Center he co-directs with Carol A. Miller, a pathologist in the Keck School of Medicine of USC, Finch uses brain cells from lab rats and mice to study tiny changes in cell structure under various conditions. Laboratory animals like rats, mice, fruit flies and worms are the preferred models for this kind of basic research (and most other medical research) because they are short-lived, reproduce quickly and are easy to handle.
Yet Finch accuses biologists of taking the easy way out when it comes to studying aging in the animal kingdom. He believes they should also be looking at longer-lived animals: turtles, birds or slow-moving rockfish that can live more than 100 years at the bottom of the sea.
“I don't know of anyone in science who has a broader knowledge base than he does. If you have a question about anything from molecular biology to the longevity of fish to the evolution of aging, call on Tuck."
These animals exhibit something called “negligible senescence,” meaning they don't seem to suffer age-related breakdowns in body processes and organs the way humans do.
In his first book more than 10 years ago, Finch suggested that the earliest vertebrates (animals with backbones) either didn't age at all or aged so slowly that the process was insignificant. Rapid aging is a recent evolutionary strategy, he argued – one that a few animals seem to have bypassed. The Blanding’s turtle, a black-and-yellow-spotted amphibian found in ponds across the Midwest and southern Canada, is one such renegade studied extensively by University of Georgia ecological scientist Justin Congdon. Since the 1950s, thousands of these 5- to 8-inch turtles have been marked and released into a reserve in southern Michigan. Research has shown that the turtles are living into their late 60s and have exactly the same mortality rates during their entire life. Humans, by contrast, have varying mortality rates throughout their life span – the safest period being age 15, when the chance of dying is about one in 2,000 in developed nations. By age 50, human mortality is one in 70 per year.
Basically, the Blanding’s turtles don't age and die like we do. While they do succumb to bacterial infections, viruses and accidents, they don’t get cancers or other sorts of diseases of aging. Other long-lived creatures include the slow-aging seagoing albatross, which can live up to 80 years. Or the yellow-eye rockfish. These deep-ocean dwellers have been known to live 140 years and still reproduce.
What these animals have in common is an ability to stay away from predators – by flying, hiding in a shell or living in tough environments. But they also possess some kind of internal protective mechanism, the ability to shield their cells from oxidization and cell death.
Generally, species that consume the most energy and oxygen live shorter lives. But some animals break the mold. Birds have high metabolisms, burn lots of oxygen, yet outlive mammals several-fold. These are the animals that negligible senescence researchers are targeting. Finch has been the leading proponent in this emerging field. He frequently collaborates with animal biologists on research studies and serves as a tireless advocate for government funding. In USC’s Symposium on Organisms with Slow Aging, a scientific conference Finch has organized yearly since 1997, wildlife biologists, neuroscientists and medical researchers come together to examine the different strategies that long-lived animals use to fight aging. Finch has long advocated setting up tissue banks to preserve and distribute cell samples of these important species. Such banks are especially important as many of these species, with the low birthrate attendant upon long life span, are endangered or near extinction from human encroachment and overharvesting.
“It's so completely contrary to what people have been focused on,” Finch says, of negligible senescence research. “The main lab-based research has focused on organisms that are short-lived so you can study them within your grad students’ time in your lab. There's been a huge emphasis on flies, worms and mice, which have a rapid aging pattern. But humans have extremely slow aging patterns. So let's look to see if there are other organisms that have very long life spans and don't show any signs of aging at all.”
Finch admits there are great obstacles to this line of research. Keeping rockfish alive in a fish tank is extremely difficult. And government funders have either balked completely at the idea, or only supported short-term studies. The next logical step is to take information from long-term field studies to the level of rigorous laboratory-based analysis. That, in turn, will tell us more about our own aging processes.

Photographed by Joe Pugliese

 

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