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Caleb E. Finch
Neurobiologist and gerontologist
If one considers only
officially authenticated public records, the longest-lived person
known was Jeanne Calment, a Frenchwoman who died in 1997 at the age of
122, infirm but "spirited and mentally sharp until the end," as
CNN.com (August 4, 1997) reported. According to CNN, "Calment credited
her longevity to Port wine, a diet rich in olive oil, and her sense of
humor." Scientists who specialize in gerontology, the study of the
processes of aging, however, believe that the secrets to her
remarkably long life were far more complex. The neurobiologist Caleb
E. Finch, a pioneer in gerontology, has been working for more than
three decades to discover the secrets of longevity--particularly those
connected to the physiological aspects of aging. When he began his
research, in the early 1970s, the accepted wisdom was that aging was
"an intractable area, just a bunch of diseases," as Finch told Jane E.
Brody for the New York Times (May 20, 1997). Even if illness
were avoided, it was widely assumed, human cells could divide or
replenish themselves only a finite number of times, and metabolism
could continue only for so long; thus, every person was in effect
programmed to die at a certain age. Once, when Finch was a graduate
student at Rockefeller University, the Nobel Prize–winning pathologist
Peyton Rous, a longtime Rockefeller researcher, asked him why he was
"wasting [his] time" looking into the processes of aging, according to
AARP Magazine (March/April 2003). "Everyone knows that aging is
mainly about cancer and vascular disease!" Rous declared to him. But
Finch disagreed; as the same magazine quoted him as saying, "I had
already convinced myself to the contrary." As he recalled to Jane
Brody, he had come to believe that "there were colossal questions
[regarding aging] that had not been approached precisely and
aggressively." "Clearly there are multiple forces and mechanisms at
work in determining life span," he told her. Paraphrasing Finch, Brody
wrote, "The rate of aging is most likely a function of gene expression
[that is, detectable effects of genes] interacting with the
environment"—"environment" in the broadest sense, ranging from weather
and air pollution to working conditions, foods eaten, and, for women,
the physiological conditions associated with pregnancy.
Finch has even questioned
the widely held idea that declining physically after several decades
is the fate of all living creatures (other than one-celled organisms,
which, by repeatedly and endlessly dividing, may be said to have
limitless life spans). Among plant species, individual giant sequoias,
bristlecone pines, and creosote bushes have survived for thousands of
years; among animal species, scientists have found 220-year-old quahog
clams, 200-year-old giant tortoises and bowhead whales, 150-year-old
orange roughy (a type of fish), and 120-year-old turkey buzzards, to
name just a few of those capable of reaching highly advanced ages.
Moreover, rockfish and painted turtles, among other very long-lived
creatures, remain vigorous and fertile into their 70s and beyond.
Finch has suggested that such organisms might escape altogether the
deterioration associated with aging—and perhaps even death, were it
not for fires and deforestation by humans, in the cases of trees, and
predation, accidents, or environmental destruction, in the cases of
animals. "We're finding new examples of this phenomenon all the time,"
Finch told Linda Marsa for the Los Angeles Times (January 5,
2004).
In a 1997 conversation
with Jane Brody, John W. Rowe, who was then president of the Mount
Sinai Hospital and Mount Sinai School of Medicine and had worked with
Finch on the MacArthur Foundation's project on aging, noted three of
Finch’s outstanding characteristics as a scientist: first, "his
vision. He can almost see around corners in terms of the direction in
which aging research is going." Second, "his openness to new ideas.
Scientists tend to have very closed channels in which they work." And
third, "his remarkable capacity to translate basic science and
evolutionary biology into the everyday life of an older person by
linking basic research to clinical needs." Finch has worked at the
University of Southern California (USC), one of the world's leading
private research universities, since 1972; he has held an endowed
chair there for 20 years and the highly prestigious title of
University Professor for 15. An internationally renowned researcher
into the causes of Alzheimer's disease (now also called Alzheimer
disease), since 1984 he has directed or co-directed the Alzheimer
Disease Research Center, which is funded by the U.S. National
Institute of Aging and located on the USC campus. Referring to Finch
by his nickname, Edward L. Schneider, who was then the dean of the
Ethel Percy Andrus Gerontology Center at USC, told Eric Miller for
USC Trojan Family Magazine (Spring 2002, on-line), "Tuck is the
world's most recognized scientist in the field of aging research. I
don't know of anyone working in the science of aging--or in any
science, really--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."
Finch has written or
co-written more than 350 scientific papers and three books—Longevity,
Senescence, and the Genome (1990), Aging: A Natural History
(with Robert E. Ricklefs, 1995), and Chance, Development, and Aging
(with Thomas B. L. Kirkwood, 2000); he has edited or co-edited 17
other books, among them Biology of Aging (1978), Between
Zeus and the Salmon: The Biodemography of Longevity (1997),
Clusterin in Normal Brain Functions and During Neurodegeneration
(1999), Cells and Surveys: Should Biological Measures Be Included
in Social Science Research? (2001), and Brain and Longevity
(2003). He has contributed to The Encyclopedia of Aging: A
Comprehensive Resource in Gerontology and Geriatrics, which has
appeared in three editions, most recently in 2001. Finch is an
accomplished fiddler and has performed and recorded traditional
Appalachian mountain songs as a founding member of the Iron Mountain
String Band.
Caleb Ellicott Finch was
born in London, England, on July 4, 1939. His parents, Benjamin F.
Finch and the former Faith Stratton, immigrated to the United States
later that year and raised him in the Hudson River Valley, in southern
New York State, and Connecticut. In the Scientist (January 25,
1988, on-line), Finch recalled that even as a young child he felt
curious about the process of growing old. His curiosity was sparked in
large part by the presence of an unusual number of very elderly people
among his relatives (one of his great-uncles, for example, lived to
the age of 103) and the tales some of them told about their lives in
the previous century and about their (and his) ancestors from as far
back as the 1770s and ’80s. His mother, who was still physically
active and mentally alert at 90, as he told Jane Brody, "fostered my
omnivorous appetite for bizarre knowledge." In about 1957 Finch
entered Yale University, in New Haven, Connecticut, where he majored
in biophysics. Thanks to a "scholarship job" on campus, as he put it
in the Scientist, he became friendly with several accomplished
professors in the Biophysics Department, among them the microbiologist
Carl Woese, the structural biologist and crystallographer Donald
Caspar, the biophysicist Richard Setlow, and the physicist Ernest C.
Pollard. "They included me in many free-wheeling discussions about the
remarkable prospects for moleclar biology that made me boil with
excitement. In one session, . . . Carl said, ‘Why don’t you study
aging? Nothing is known, and you are crazy enough to try.’" Finch
continued, "I was also much influenced by two courses, Pollard’s on
thermodynamics and Setlow’s on atomic physics, which stressed how
crucial assumptions are to building theories. Like many others, I
hoped that rigorous and comprehensive theories on molecular biology
could emerge by using approaches that were so effective in physics."
After Finch earned a B.S.
degree from Yale, in 1961, he entered Rockefeller University, in New
York City, to pursue a Ph.D. in cellular biology. Within the next two
years or so, he began working there in the laboratory of Alfred
Mirsky, whose wide-ranging research then focused on gene regulation,
about which the first discoveries were being made; one of his fellow
lab workers was the young cell biologist Eric H. Davidson. Mirsky and
Davidson "greatly helped to formulate my ideas about aging," Finch
wrote for the Scientist. After a number of attempts, he
succeeded in breeding a particular strain of mice whose members were
long-lived and resistant to illness; these mice resembled one another
genetically far more closely than they did unrelated mice. (He has
used later generations of the same colony of mice in his research to
this day.) When the oldest of the mice were no longer young (in mouse
years), he set about studying aspects of their cellular activities.
Having remembered seeing, as a child, elderly relatives shivering in
temperatures in which he himself did not feel cold, he devised an
experiment in which he exposed both old and young mice to cold, with
the goal of determining whether their physiological reactions to the
cold differed and, if so, whether the differences could be attributed
to changes in genetic expression in the older mice. He did so by
measuring the presence in each mouse's blood of an enzyme produced in
the liver called tyrosine aminotransferase. It was already known that
production of that enzyme is sparked by the presence in the blood of
particular hormones that are secreted by endocrine glands (in this
case, the pituitary and adrenal glands) as needed--for example, to
warm the body when its temperature falls below a certain point. Finch
showed that when he induced the production of the enzyme not by
exposing the mice to cold but by manipulating the hormones so that
they acted directly on the liver, young mice and old mice produced the
enzyme at the same speed. By contrast, when the mice were exposed to
cold and experienced what scientists refer to as cold stress, the
younger mice produced the enzyme significantly faster than the older
ones. (The older mice would thus feel cold long before the younger
mice did.) Since the actions of hormones are regulated by genes,
Finch's experiment showed that the same genes had caused different
effects in the two sets of mice. He reported his results in 1969,
shortly after another scientist, the biochemist Richard C. Adelman,
had reported similar results with experiments involving a different
enzyme. Finch's finding that "gene functions could change with age,"
as he wrote for the Scientist, suggested to him "the hypothesis
that neuroendocrine age changes could cascade to many other cells." He
added, "Adelman and I were lucky to report similar results within a
few months [of each other] . . . , because we few researchers often
waited years before data were replicated."
Finch remained at
Rockefeller as a guest investigator until 1970, then spent two years
as an assistant professor at Cornell University Medical College, also
in New York. In 1972 he joined the faculty of the University of
Southern California as an assistant professor of gerontology. He
served as an associate professor from 1975 to 1978, when he was
promoted to professor of biological sciences and neurology; since 1985
he has held the title Arco and William F. Kieschnick Professor of the
Neurobiology of Aging (named for the Atlantic Richfield oil company
and one of its former executives), and since 1989, that of University
Professor (an honor currently held by only a dozen others at USC).
At USC Finch has
investigated the anatomical and functional relationships between the
brain and the endocrine system. Using rats and mice as well as human
subjects of various ages, he studied changes in the rates and
quantities of catecholamines (for example, epinephrine and
norepinephrine, which are produced in the brain and transmit signals
between nerve cells) to help to explain why some neurological diseases
in adults usually occur at particular ages. Through the years Finch
has also given much thought and devoted many of his research hours to
trying to determine the causes, understand the progression, and find
ways of preventing or slowing the ravages of Alzheimer's disease,
which currently affects roughly 4.5 million Americans and consumes
more than $100 billion a year in health-care costs in the U.S.—figures
that may quadruple within a few decades, according to Linda Bren in
FDA Consumer (July/August 2003, on-line), as the more than 60
million Americans ages 45 to 64 in 2002 grow older and survive to more
advanced ages than previous generations. Currently, nearly half of
people ages 85 and over suffer from Alzheimer's, which is marked by
memory loss and mental confusion and is invariably fatal. One symptom
of Alzheimer's (as determined through microscopic analysis of the
brain after death, which is the only way to diagnose the disease with
certainty) is the formation within the brain of plaques (dense, sticky
accumulations of a protein called beta-amyloid) in spaces between
nerve cells, and tangles (snarled masses of threads, or fibrils, of a
protein called tau) inside nerve cells; another symptom is the
overabundance of the enzyme cholinesterase and the resulting
deficiency in the neurotransmitter acetylcholine. Finch discovered yet
another: the presence of so-called inflammatory proteins (which
scientists previously thought did not occur in the brain) that produce
a new form of amyloid (a type of protein) called amyloid ß derived
diffusible ligands, or ADDLs (pronounced "addles"), which can spread
throughout the brain and appear to be toxic. Further experiments
showed that a substance known as APO-J, or clusterin, could prevent
ADDLs from forming plaques, but it also disrupted neurons' capacity to
transmit signals to one another. Along with the molecular
pharmacologist and biochemist Grant A. Krafft and the neurobiologist
William L. Klein, Finch set up a company called Acumen
Pharmaceuticals, whose goal is to create a vaccine to prevent
Alzheimer's; the company recently formed a partnership with the giant
pharmaceutical company Merck. Finch has also found evidence that
people who have taken anti-inflammatory drugs, such as aspirin or
iboprufen, for long periods (in the hopes of preventing heart attacks,
for example) are less likely than others to develop Alzheimer's. Other
studies conducted by Finch have tentatively linked antioxidants to
Alzheimer's-related neurological deterioration and have revealed
connections between hormone replacement therapy—specifically, the
hormone estrogen—and the possible delay of onset of, or even
prevention of, Alzheimer's.
One factor that makes
research in longevity inherently difficult is plain: studying
long-lived animals as they grow older requires an investment of many
years. Others are less obvious. As Finch explained to an interviewer
for Living Longer and Loving It (Spring 2001, on-line),
published by the Alliance for Aging Research, "We know that there are
families with a rare genetic history of early-onset Alzheimer's,
diabetes, cancer and heart disease—families whose carriers of these
strong genes die before 50. Some of these diseases show up later in
the general population as well, and when they show up later, we don't
know if there is a strong genetic effect. There also are people who
have two copies of a ‘bad’ gene who live into their 80s, 90s and more
without ever getting the disease. So we don't know if the absence of
disease is due to lifestyle or the effect of some other gene or genes.
There are many complicated questions that must be answered before we
really understand the relationship between genetics and disease." When
the interviewer asked him, "How is longevity related to genes, and how
much can be attributed to environmental and lifestyle factors?" Finch
responded, "If you look at longevity itself, and not disease, you find
that identical twins, by the time they're 80, have no closer life
spans than other members of the general community in which they live.
So you might draw the conclusion that after a certain age, genes have
a relatively weak effect on life span. On the other hand, there are
families whose members seem to have an unusually long life span
despite environmental factors. Overall, about one-third of life span
within a species can be associated with particular gene differences
between individuals. We don't know what the other two-thirds is yet.
Is it the environment interacting with genes? We just can't tell yet."
Finch has contributed more
than 350 articles to professional journals; in 1991, according to
Science Watch (May 1991, on-line), as measured by the number of
times other researchers cited papers of his that were published from
1981 to 1990, he ranked among the top one-half of one percent of
scientists internationally. Among other honors, Finch has won the USC
Associates Award for Creativity in Research and Scholarship, the
Robert W. Kleemeier Award of the Gerontological Society of America,
and the Brookdale Foundation Award for Distinguished Contributions to
Gerontology through Research in Biology (all in 1985); the
Allied-Signal Inc. Award for Achievement in Biomedical Research on
Aging (1988); the Arthur Cherkin Memorial Award, from the University
of California at Los Angeles (1991); the Sandoz Prize, the premier
award of the International Association of Gerontology (1995); and the
Irving Wright Award of the American Federation of Aging Research
(1999).
A serious fiddler for 44
years, Finch formed the Iron Mountain String Band with Eric H.
Davidson, who plays banjo, and others in the 1960s; since the early
1970s, the band has been a trio, with Brooke Moyer as guitarist and
singer. Three of the group's albums--The Iron Mountain String Band:
An Old Time Southern Mountain String Band (1973), Walkin' in
the Parlor (1975), and Someday We'll Meet Again (1981), are
Folkways releases; the fourth, Songs of Old Time America
(1998), recorded in 1981, came out on the Peach Bottom label. Much of
the inspiration for the group's music comes from their collection of
field recordings, made by Davidson, Finch, and others in Virginia and
North Carolina for 30 years ending in the 1980s; a dozen of those
recordings, released on the Folkways/Asch label, are now distributed
by the Smithsonian Institution. The band has performed widely, at
festivals, colleges, clubs, and bars and on the radio; it played the
music (composed by John Rubinstein) for The Dollmaker, a 1984
made-for-television movie that starred Jane Fonda.
In 1975 Finch married
Doris Nossamen, a fabric artist; he is stepfather to her two adult
sons, Michael Tsongas and Alec Tsongas. Finch told Jane Brody that he
has "an excellent intellectual navigation system" and enjoys
"exuberant stress." "I believe in going hell-bent for leather," he
said, "as long as you don’t do yourself in if you feel tired or sick."
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