Interview with Paola Timiras, Professor Emeritus, Department of Molecular and Cell Biology
Number: 00S06. Issue: Spring 2000
Author[s]:
Charity Kirk, Nahal Lalefar, Grace Liao, Jennifer Lin, and Viet Nguyen
Keywords:
Abstract:
Professor Paola Timiras, M.D., Ph.D., has been with UC Berkeley for over forty years. During this time, she has helped bring aging research to the forefront of science and medicine.
She has also lectured (MCB 135: Physiology of Aging, and the IDS 114 Series: Advances in Aging) and written many books on the subject, including most recently, a Laboratory Manual of Studies of Aging (July 1999).
She has traveled extensively and shared her research with colleages from around the world. She has had a strong influence on her students and those around her, including her daughter, who has followed in her footsteps and is now a geriatrician and lecturer at Columbia University.
Professor Timiras believes that aging is a continual process influenced by both genetic and environmental factors. She believes that the goal of aging research is not only to extend the lifespan, but to improve the quality of life as well.
And at the age of 76, she is living proof that age is nothing but a number.
BSJ: As a child growing up in Italy, did you always have an
aspiration to become a doctor, a researcher, and a professor? Did you have any
other aspirations? Who were your influences and role models?
Dr. Timiras: As long as I can remember, I wanted to become a
physician. I did not know that there was such a thing as a researcher. But a
"doctor," I knew very well. I had no other particular aspirations. My
grandfather who had graduated from medical school in l865, had been a
well-known physician, director for many years of the department of dermatology
and venereal diseases (as STDs were called one century ago) at the University
of Rome and a pioneer, almost a "missionary," in the prevention of
such diseases through education.
My uncle was a physician, also
very well known in Rome, a specialist in metabolic diseases such as diabetes.
It seemed logical to me from the very beginning that I was to follow in my
grandfather's and uncle's footsteps. They were both more important to me as
role models than my father, who was a
demographer and also involved in Italian politics. As an active opponent of the fascist movement that had overtaken
the Italian government in the l920s, he left Italy as a political expatriate in
l924, lived and worked in France until his return to Rome in 1946, at the end
of W.W.II. I was not exposed to his influence much. Becoming a physician was what I wanted to do. There was no other
choice for me when I entered the university, although, I changed my mind later
on.
BSJ: You graduated from medical school in 1947, obtained
your Ph.D. in experimental medicine and surgery in 1952, and began teaching at
UC Berkeley in 1958, where you have remained ever since. Those are outstanding
accomplishments. Did you ever feel that you had to overcome many obstacles to
attain such goals, especially at that time ? when women were not typically
involved in medicine?
Dr. Timiras: Yes,
there were difficulties as in everybody?s career, and probably more so in my
case, as a woman and immigrant (first in Canada and the in the U.S.). At the
University of Montreal in Canada, where I was a postdoctoral from l947 to l952,
during the qualifying examination of one of my classmates, he was asked the
question, "How do you rate performance and potential of the other students in your program?" It was a very illustrious class with, among
others, Dr. Roger Guillemin, who received the Nobel Prize in 1977 for his
discovery of the hypothalamic hormones. We were all very good young
investigators. When my colleague had completed the qualifying examination, we
all clustered around him to inquire whether or not he had passed (which he did)
and what questions he had been asked.
With a big smile, he told me, "You know, they also asked me about
you. And I said "for a woman you were okay." He said that as if it was a great compliment
to me and I should be happy with that.
Here at the University of
California, I was appointed in l958 together with another professor [who
was male]. Over the years, we were
promoted together, so I did not feel
that there was any prejudice against women, even at that time. It is possible
that I could have advanced faster if I had been a man, but I do not know. I never experienced any prejudice, not
openly, neither at UCB nor in the department of Pharmacology at the University
of Utah where I was from l953-56.
BSJ: In your opinion, how has the role of women in science
changed throughout the decades that you have been involved in science?
Dr. Timiras: What you may not imagine, and I did not realize
myself until recently, is that, in medical school, the greatest difficulties
were not with the other students nor the professors. The difficulty was with
the patients. For example, I remember,
that whenever one of us girls (there
were 10 girls in a class of 200 medical students) would come close to a
patient' s bed, there would be protests. The nurse would be called, "Who
is this girl? What does she want?"
These were the reactions of patients (most with a limited education) in
public hospitals. It was difficult for
me. I was intimidated. In l947, when I graduated, I decided not to pursue a
clinical career.
Overall,
during the last 50 years it seems that women have been more accepted and
trusted as proficient in the medical profession as well as in biomedical
research. Or is it possible that women
themselves have evolved, are they, perhaps, more confident? I believe that it
is up to you, the new generation, to show how good you are. For example, my
physician is a woman, in fact, she graduated from the Health and Medical
Sciences Program [at UC Berkeley].
Still prejudice against women persists among men and even women. In many
parts of the world, both men and women prefer to be treated by a physician who
is a man. The acceptance of
professional women has improved and will continue to do so because of the
overall better general education of the population. As far as I am concerned I
[do not regret having opted] for an academic and research career.
BSJ: In addition to being a doctor, researcher, and
professor, you are also the author of several books on geriatrics and
gerontology. Why do you write, and how do you think it adds to your life?
Dr. Timiras: I like to write very much. I like to organize
[my] thoughts and present the available information as clearly as possible. I
enjoy to go over in my mind the material of my lectures or books and strive to
present it in a manner which is not only understandable to many but also may
excite their enthusiasm. It gives me
great satisfaction to do it. It certainly adds to my life, and if I were not to
teach, I would continue to write. This past July, 1999, I edited A Laboratory
Manual of the Studies of Aging with a colleague. I am now considering undertaking a third edition of my book,
Physiological Basis of Aging and Geriatrics,
the second edition of which was published in l994.
BSJ: With aging comes the issue of more and more people
spending more of their lives in retirement. What kind of effect do you think
this will have on society?
Dr. Timiras: It may
have a deleterious effect unless we vigorously muster all our biomedical and
societal resources to better understand (treat and prevent) not only the
diseases associated with old age, but also the basic processes of aging. It is
in the interest of the society at large to promote better health and to provide
the "successful" elders with sufficient activities so they do not
deteriorate and may continue to contribute to the benefit of all. For example, in one of the last issues of
the Berkeleyan, there was an article [about] the university launching a billion
dollar initiative in the health sciences for this coming year 2000. I eagerly read the article but was
disappointed that little was planned about amplifying the study of development
and aging. This is an important area of study. I believe the most important
goal for research in humans should be to better understand how physiological
competence is achieved during development through genetic and external
influences, how it progresses during adulthood in response to environmental
demands and how well it can be maintained in old age. With the lengthening of
the human life span, I?m not the only crazy one who, at my age, insists on
wanting to work here at the university and traveling around the world to share
research data with other scientists.
Several people do the same; if you?re in good health, why not?
The study
of the diseases of old age is important, but equally or more important is
preventing the occurrence of disease by strengthening physiological competence
at all ages and thereby optimizing mental and physical ability to live
independently and contribute to the progress of humankind. I believe that it is my duty to contribute
as much and as long as I can to the mission I have chosen in life to provide
new biological data for education of the new generations.
BSJ: How do you feel about your own desire to continue
teaching past the age where people typically retire? How has aging personally affected your life and work here at UC
Berkeley?
Dr. Timiras: As I
said before, I do not believe that aging has greatly affected my goals so
far. Maybe it has relieved me of the
major anxieties. In the life of the
university researcher, one of the [major concerns] is to find funds to support
research. Funds are necessary to
contribute to the advancement to one's field of interest. For example, one of the significant
contributions of my laboratory was, in the early l970s, the identification of
the mechanisms by which thyroid hormones promote brain development. Our studies as well as those from other
laboratories have shown that babies born with low thyroid function are at risk
for a very severe form of mental retardation known as
"cretinism". If, however,
hypothyroidism is detected at birth and immediately corrected by administration
of the hormone, then the baby develops normally both mentally and
physically.
These
studies were quite expensive and application for research funding was an
ongoing task for me. Likewise, one's
research must result in a sufficient number of good publications to advance
one's career. In my present conditions,
I can relax. I have enough experience and equipment to still continue to carry
on some significant research but in a calmer atmosphere, so it is more
pleasant.
BSJ: Some claim that the focus of researching on aging is
now more centered on why we age rather than diseases related to aging, which
was the focus in the past. Others argue that the main goal of aging research is
not to extend the human life span, but rather, to make the final decades of
people?s lives more active by lessening the occurrence of diseases associated
with aging. With which viewpoint are
you more inclined to agree?
Dr. Timiras: Research is now more centered on why we age,
how to understand the fundamental cellular and molecular mechanisms of aging,
how we may prevent some of the diseases of old age by improving normal function
at all ages. The goal is not primarily
to extend the human life span. If we
can extend it, yes, but only if we can extend it in good health, not to be completely
incapacitated for many years of our lives.
Even in
geriatrics, the medical branch interested in aging, the goal is not only to
treat the diseases of old age, but also to have an early physiological
assessment of the individual, and on that basis, to suggest a program to make
this person be well as long as possible.
Education
of one's body and function is important at all ages, but particularly at the
two extremes of life: during development when genetics directs the maturation
of function, and in old age when the environment continues to mold the
individual's phenotype and to control risk factors.
BSJ: How do you believe hormones affect the aging process?
Dr. Timiras: Well, certainly some of the hormones are quite
obvious, for example, estrogen and menopause.
At the time of menopause there is a change in both reproductive function and in the function of the whole
body due to the failure of the ovary to secrete estrogens. And also equally
important is that some of the many important functions controlled by estrogens
can be restored by hormonal replacement therapy. But there might be some other hormones, perhaps some local
hormones that we do not know about yet, which can also affect aging of
cells/tissues.
For
example, it was considered that neurons could never regenerate or divide. But now we know that is not true. And we know for example that local
administration of a nerve growth factor will facilitate the regeneration of
neurons. In the view of potentially
more modifiable neurons, hormones like estrogens may have an effect in
improving the condition of neurons, even at old age. And, indeed, there is now increasing evidence that estrogens and
other hormones may delay the appearance and/or reduce the severity of
neurodegenerative diseases associated with old age.
Another
example of hormonal changes that has become more and more frequent in the
elderly is the late onset of diabetes (also called non-insulin dependent
diabetes) that occurs among older people. Even though the levels of insulin are
fairly normal, they are not sufficient to maintain normal glucose levels.
BSJ: How would one go about preventing these changes, if
they can be prevented?
Dr. Timiras: Well, we should know more about the mechanisms
of action of hormones. For example, one
of the recent advances in estrogen replacement therapy is the identification/synthesis
of compounds which bind to the same receptors as estrogen but not in all
tissues where there are estrogen receptors; rather, they are more selective for
certain cells or tissues. As you know,
one of the disadvantages of hormonal replacement therapy with estrogen is that
in some cases it may facilitate the development of breast and uterine
cancer. That is because the replacement
estrogens will bind to the receptors in the mammary gland or the uterus. But there are some new compounds, the
so-called SERMs, selective estrogen receptor modulators, which theoretically
would bind selectively to only one group of receptors so we will have a more
localized action as needed; for example, for women who have severe osteoporosis
or women who have high cholesterol.
BSJ: What advice would you give to the undergraduates and
the younger generation as a whole, on how to age successfully? And what are you
personally doing in your life to slow the aging process? Caloric restriction?
In take of antioxidants?
Dr. Timiras: Now, that is a very good question because I was
one of the first to publish, in 1972, a book, Developmental Physiology and
Aging, which related early development (from fertilization to young adulthood)
to aging. The idea is that, in life, we have a continuum of events and each
successive event is related to the previous one; so, if you want to age
successfully, you have to have a good developmental period. I think that this
is the wisest way to think about aging. Of course, a child or an infant will
not think about aging, but the parents should keep in mind that ensuring the
good health, growth, and development of the child also ensures his/her
successful aging.
Caloric
restriction effectively lengthens the life span of rats and mice but has never been tried in humans, and I do not
know if it will ever be tried. Even if [antioxidants] are successful at any
age, if one can demonstrate that they promote health ? which has not been
demonstrated in humans ? then one should consider preventing oxidative damage
starting from an early age and not just when one is 65.
BSJ: Recently, there has been more attention focused on the
idea of a person?s real age vs. their chronological age. Do you believe in the
fact that there might be a difference between the two? If so, what kind of
difference is there?
Dr. Timiras: Well, I would argue that [idea] is not recent.
[It has been] well known for a long time that some people look younger than
their age, and some people look older than their age. We have not spoken here
at all of genes and, as you know, longevity is hereditary. There may be a very
strong genetic component which makes some people have a longer and healthier
life. In some lower species, some gene or a group of genes have been identified
that may either shorten or prolong the life span. Generally, one says the best way to live longer is to choose
parents who lived longer. So, I?m very happy that my grandparents and my
parents lived quite long; I hope that I have inherited their longevity genes.
BSJ: In the U.S., there are many stereotypes placed upon
seniors, such as the elderly not being productive in society. You have studied
and traveled around the world; in your opinion, do these stereotypes exist in
other countries or is it just those in the U.S. who maintain this type of
attitude?
Dr. Timiras: As always, especially when we speak of social
factors, there are many nuances. It has been said that the US society is mostly in favor of youth;
you want to be young in all possible ways. However, there are some human
societies where older people have great prestige. Currently, with the greater
motility of populations across the globe, we are witnessing many changes. For
example, changes in the views of when people are considered old--now 41 is not
an old age, but it was at the turn of this century when the average life span
was 45 years. First of all, the length
of the life span has changed and the attitude towards older people is also
changing. I think that education is the most important means to induce these
changes; the university, students
and professors alike, should work
together to educate people and change their attitudes.
Also,
another aspect is to offer older people more possibilities to diversify. There
are many countries [that have programs for older people]. For example, I was
head of the UC program abroad in France for two years. In France, every university has a very
popular program for the older generation which offers courses to both educate
and re-educate interested older people. So, it is important [to support older
people]; that is why I insist that it is a very important education function of
the university.
BSJ: Is there any truth to the saying that "To be old
is to be sick?"
Dr. Timiras:
Unfortunately, you may be sick at all ages, not exclusively because you are old. [However], it is true that in old age you can be more sick more
frequently and more severely than at young ages. But also, at very young ages
you can be more sick and more severely sick than in adult or young adult age.
It is true that one can be old and sick, but it is not necessarily so. And, of
course, as one gets older and older the incidence and severity of diseases
increase, but you can also age "successfully," i.e. remaining in good
health and good function until very old age. The concept of "compression
of morbidity" suggested by many investigators implies that individuals
will live well until old age and then suddenly die after a very short and acute
disease.
BSJ: Do you think that we will ever find a way to slow the
aging process significantly?
Dr. Timiras: Oh, yes I believe [this]; I am very optimistic
in this respect
BSJ: The October 1997 issue of Aging suggested that by the
year 2027 the average person will live to be over 100 years of age. Based upon
your research and personal knowledge, will it be possible, in the future, to
increase the average human life span past the century mark?
Dr. Timiras: I certainly believe that it is possible. The
question is not if it is possible, but "is it desirable?" During the early years of my working in
gerontology, let us say the past twenty to thirty years, I read very few
studies on centenarians. Now, you look
at [recent] publications on any aspect or function in the elderly and you have
find many papers on centenarians. These
studies are based not on a low number but on 200-500 centenarians, so the
number of centenarians [is increasing] rapidly. It is not unlikely that in 2027
[the average person will live to] be a centenarian. Yet, how well these centenarians
will function, that is what we have to work on, not so much as how many
centenarians there will be.
So far, the
oldest living person was a French lady, Madame Calment from the city of Arles,
in Southern France; she lived to be one hundred twenty-two years of age. And
apparently, she was rather competent. Her hearing was not very good, but if one
asked questions loud enough [she would answer] appropriately. Therefore, it is
possible [to live a long time and be competent]. She died when she was one hundred
twenty-two and, I understand, she was very energetic. She had her own will
until the very end.
BSJ: In your opinion, how long should humans live?
Dr. Timiras: As long as they are in good health.
BSJ: Please define "successful" or
"healthful" aging.
Dr. Timiras: As you know, you do not have to go very far or
think very hard to answer this question. In fact, there is even a book on
successful aging which was published in 1999 by Doctors Kahn and Rowe just
entitled "Successful Aging". According to this book, the elderly do
not represent an homogenous group but show great heterogeneity. There are three major trajectories of life
span. One trajectory, "aging with disease," considers individuals who
are sick with one or several illnesses that may have started in middle age and
progressively become more severe as the individual ages. The second trajectory, "usual
aging," comprises individuals who may not be affected by major diseases
but have a decline in normal function. And the third trajectory of "successful aging" includes those
individuals who have no diseases and also continue to have a good functional
ability. I am sure you know many successful aging people who can continue their
activities quite well and have no major impairment. So, theoretically, it is
possible to be a centenarian and a "successful" centenarian. That
would be the way we all would like to age.
BSJ: There is an award given in your name to two students a
year doing outstanding research in the field of aging, and you teach a class on
aging. What else are you doing to support aging research and help educate the
public?
Dr. Timiras: I am very happy to say that I have always tried
to educate all the students who have worked, and those who are currently
working, in my laboratory, to view the life span as the continuum of
physiological events directed by genetic make-up and influenced by
external/internal environmental factors. I am happy to state that the many
students who received a Ph.D. with me and most of my many post-doctorals have
been following and improving upon my general concepts of physiology. Most of these students are conducting
research and teaching courses in development and aging. Recently one of my former graduate students,
together with one of my former post-doctoral [students], gave the University a
relatively rich endowment to continue studies in aging. You can do a lot by
establishing guidelines for a school of thought that addresses the entire
organism, not only molecules, and how this organism fares/ responds in the
surrounding environment . That is why I
say education is very important. I participate to scientific meetings on
development and aging. Recently, I am sure you have heard that there is a new
research institute on aging the Buck Center on Aging in Marin County. I was kindly invited to its inauguration.
Three of my former graduate students and two or three physicians were there,
and several of them told me "We took your class on aging and that is what
made us decide to [study] geriatrics."
Those are
ways in which you can support aging ? to do your research and to go around the
world. I was in China this summer for a meeting of the Chinese Physiological
Society; I was speaking on my research on the role of estrogen in regulating
the function of glial cells which, in turn,
regulate the function of neurons. You try to spread the good word
everywhere you can. You can write books. In India, for example the life span
has increased considerably, but is still much shorter [in comparison] with
[that of] this country. Yet, there are now
courses on aging there and
active research on aging processes.
In Europe,
everybody is aware of the importance of aging. For example, l999 was designated
"The Year of the Older Person" [by the United Nations].
BSJ: What are your plans now as a professor emerita?
Dr. Timiras: Well, I plan to do as much as I can [of] what I
am doing now [for] as long as I can.
BSJ: Where else have you traveled besides Spain and France?
Dr. Timiras: Well, I [have been to] Japan many times. That is
a country I like very much. Unfortunately, I cannot speak Japanese but I was
there five times. I have many former students residing in Japan who are working
in the area of gerontology. I was in India several times; even there, people have started to organize
programs and being interested in aging. The life span was very short until
30-40 years ago, but now it is lengthening. I have also visited Iran; many of
my students are from Iran. There are also former students of mine from [South
American] universities in Central America and Mexico. Everywhere, researcher
and educators have become aware of the importance to address development and
aging of living organisms from a global point of view.
BSJ: You went to medical school and you got your Ph.D. in
experimental medicine and surgery. When did you start focusing on aging?
Dr. Timiras: The first textbook of aging was written before
Christ by a very famous Roman writer and orator by the name of Cicero. He wrote
De Senectute , "Of Old Age." Throughout history, people have been
interested in old age, living longer, and living well. Among specialties in
medicine, geriatrics, as a subspecialty of internal medicine or family
medicine, is quite recent. On this campus, the first courses on aging, which
were some of the earliest ones in this country, were started in the mid-1960s.
Of course, now there is much more interest in this topic.
BSJ: Do you have any family members who are also involved in
aging research?
Dr. Timiras: My daughter is a geriatrician. She was, in
fact, one of the first who passed the National Board of Geriatrics when it was
first offered. She took her residency fellowship here at Mount Zion Hospital.
Indeed, one of the first programs in geriatrics was in San Francisco at Mount
Zion. She is only one member of the family who is interested in aging. My
cousin, with whom I went to medical school, and who was a microbiologist, was
also interested in aspects of infectious diseases and aging.
BSJ: How do you think that the process of aging has changed
over the years?
Dr. Timiras: When I was a medical student, patients with
pneumonia died in the hospital one after another, after suffering ten days, two
weeks. Now, in two to three days, you take antibiotics, and you are on your
feet again. That is probably one of the greatest gifts to humankind that has
occurred during my professional life as a biologist. And of course, the fact
that you live much longer. My grandfather lived to 95, and my mother and father
also lived to age 85. I come from a family of [long] living people.
However,
living until an old age is not the norm in some societies. There are some tribes that do not have the
word menopause, because nobody reaches the age that menopause usually occurs;
therefore, to that tribe, menopause just does not exist, even as a concept. And
if a rare woman reaches menopause, that in itself is so unique that the fact
that she is no longer menstruating is a minor point. There are even languages
in which the word menopause does not exist.
Identification
of the mechanisms that regulate development and aging, from molecular to
organism levels, must be a worldwide goal, indispensable for the progress of
life on Earth.
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