Discussion

Fond memories of my years at UCLA with Roy Walford

Richard Weindrucha,b,c,*

aDepartment of Medicine, University of Wisconsin Medical School, Madison, WI 53706, USAbGeriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705 USA

cWisconsin Primate Research Center, University of Wisconsin, Madison, WI 53715, USA

Having Roy Walford as my scientific mentor and good

friend was amazingly good fortune. To honor Roy and his

incredible and diverse accomplishments, I provide this

chronology of special memories during 1975–1987 when

we worked together at the University of California at Los

Angeles (UCLA).

Meeting Dr Walford. My pre-doctoral training began in

the fall of 1975 when I enrolled in UCLA’s doctoral

program in Experimental Pathology. The program was

small with only two or three students admitted per year.

Likewise, UCLA’s Pathology Department was not large,

having ,20 faculty members, about half of whom had

active research programs.

As is still typical today, one’s thesis research topic was

selected following rotations through laboratories of

potential interest. Following brief (and non-exciting)

research experiences in labs investigating either charac-

teristics of cultured hepatocytes or the pathogenesis of

bladder cancer, I eagerly awaited my rotation in Dr Roy

Walford’s laboratory, which was investigating multiple

aspects of the aging process. My excitement was based on

three factors. First, my only prior research experience was

as an undergraduate and master’s student at the University

of Illinois (Urbana), where I studied aging in the ciliated

protozoan Tetrahymena pyriformis (Weindruch and Doer-

der, 1975). Second, I had heard only highly favorable

words said about Roy by faculty and students. Lastly, in

the eyes of a 25-year-old Illinoisan adapting to the ways

of Los Angeles, Roy was a truly cool-looking 51-year-old

guy with his trademark shaved dome, huge mustache and

unique persona.

I remember our first meeting. Roy’s office and lab were

located in a subterranean part of the hospital (not atypical

for pathologists). Our conversation began with his views

on the importance of aging research and the bright future

he saw for the area. Then he discussed several topics

within the biology of aging (e.g. dietary restriction,

immunological aging, DNA repair, genetics of longevity)

which could form the basis of a doctoral thesis in his

laboratory. Not surprisingly, all of these topics have

become major areas of investigation in biological

gerontology. Roy provided me with some reading

materials and a few days later it was very clear that DR

would be the focus of my thesis research. Little did I

know that 29 years later this would still be the main focus

of my research.

My first experiments. I became very interested in

designing new diets for DR work and did so based on the

pioneering work of Morris Ross. Indeed, his ‘Diet D’ (Ross,

1961) was the basis for what we used to feed DR mice. I also

studied the hypothermic state induced by DR and spent

many hours in the animal care facility measuring rectal

temperatures in normally fed and DR mice. Although not

very ‘high tech’, it was amazing to observe. But the main

focus during my pre-doctoral years was on immunological

aging in the context of DR. Due to the fact that Roy was so

kind as to provide me with a full-time technician (James

Kristie), I was able to complete my doctoral training in late

1978 (Thesis title ‘Effects of controlled dietary restriction

and immunoactive drugs on immunologic aging in mice’).

In Roy’s lab there was freedom to explore new ideas. The

idea that was of the greatest interest to me was the

possibility that DR started in middle age or later can retard

the aging process. Roy concurred that this made great sense

to explore and allowed me to set up populations of mice

started on DR at varying adult ages. Our plan was to use a

gradual onset of DR using nutrient-enriched diets. Some

mice were designated to be studied for longevity and disease

0531-5565/$ - see front matter q 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.exger.2004.03.032

Experimental Gerontology 39 (2004) 943–945

www.elsevier.com/locate/expgero

* Corresponding author. Address: Geriatric Research, Education, and

Clinical Center, William S. Middleton Memorial Veterans Hospital,

Madison, WI 53705, USA. Tel.: þ1-608-256-1901x11642; fax: þ1-608-

280-7202.

E-mail address: rhweindr@wisc.edu (R. Weindruch).

patterns, while others were sacrificed for immunological

studies. This animal resource led to some of our most

exciting results.

Roy was invited to participate in a symposium on

‘Nutrition and Aging’ at the 1978 FASEB meeting in

Atlantic City. He kindly asked if I would lead the effort in

preparing a manuscript (part review, part new data) from

which his talk would derive. This turned out to be a

marvelous learning experience and led to our first joint

publication (Weindruch et al., 1979). It also led to the first of

many ‘road trips’ with Roy.

My first large scientific meeting. This was an exciting

time for a 28-year-old graduate student. First, the transcon-

tinental flight (actually to Philadelphia to switch to a

commuter plane of questionable airworthiness) was a new

experience for me. Also, I had not been to Atlantic City.

Roy was a great mentor who kindly introduced me to his

colleagues (including Robert Good and Calvin Lang, if I

recall correctly). I clearly remember the symposium and the

thrill of seeing data that I had generated be discussed in a

favorable light. Another good memory was several hours of

scotch drinking with my mentor at an establishment

harboring scantily clad females. Some serious mentoring

took place during our conversations that evening.

Mitochondria. The aforementioned freedom in Roy’s lab

was also expressed by his nurturing my then new interest in

mitochondria. My curiosity was sparked by findings that

mitochondria produce free radicals as a normal consequence

of energy (calorie) metabolism (Boveris and Chance, 1973)

and that production rates increase with aging (Nohl and

Hegner, 1978). Wanting to learn about the effects of DR on

mitochondria, I had the good fortune to have Marshall

Cheung as a fellow graduate student in Experimental

Pathology. We decided to devote Saturday mornings to

measuring mitochondrial respiration in tissues from mice on

DR. This resulted in a publication (Weindruch et al., 1980),

which, to my knowledge, was the first study of mitochondria

in the context of DR. The importance of mitochondria in

understanding how DR works is also suggested by work that

we published much later showing a linear inverse

relationship between caloric intake (four levels tested) and

maximum lifespan in mice (Weindruch et al., 1986).

Adult-onset DR. In 1982, we published two reports

concerning favorable effects of DR started in mid-life or

beyond in mice. These publications were the result of Roy’s

supporting my interest in this area: the sizable colony we

had established in 1978 of mice subjected to DR at middle

age or beyond was about to pay dividends. This was an

exciting time in the Walford lab.

The first report was published in the February issue of the

Proceedings of the National Academy of Sciences (Wein-

druch et al., 1982). This paper was kindly sponsored by

Robert Good, who at the time was working with Gabriel

Fernandes to productively explore the DR’s effects in

autoimmune mouse strains. In our report we showed that

several measures of immunological aging stayed ‘younger

longer’ in mice subjected to DR at 12, 17 or 22 months of

age and tested at various ages thereafter.

The other publication appeared in the March 12 issue of

Science (Weindruch and Walford, 1982) and showed that

starting DR at 12-13 months of age in two long-lived mouse

strains led to 10–20% increases in mean and maximum

lifespans. The incidence of spontaneous lymphoma was also

reduced. This was the first clear demonstration of the ability

of DR to extend lifespan when started in middle age. It also

separated at least a portion of DR’s effects away from the

need to slow growth and delay puberty. The results would

Fig. 1. Roy Walford enjoying the party following Richard Weindruch’s

wedding on October 2, 1983.

Fig. 2. Dr Walford and Weindruch having a conversation in September,

1993 at Biosphere 2. Two weeks later Roy ended his two year stay therein.

R. Weindruch / Experimental Gerontology 39 (2004) 943–945944

be consistent with DR inducing a different metabolic state,

which yields aging retardation. We are exploring this

possibility today using microarrays to generate gene

expression profiles which provide a global view of shifts

in gene expression associated with DR (Lee et al., 2002).

Engagement and wedding parties. It was also in 1982

that I met Robin Steinhardt who became my future wife. Of

course Roy and other lab members were invited to parties

associated with my engagement and wedding. As is likely

communicated in several other contributions to this volume,

Roy loved a good party. Our engagement party was held in

Encino, CA at the home of the family who had befriended

me as a lonely, workaholic graduate student and had

introduced me to Robin. The party was a pleasant affair

attended by folks ranging in age from 25 to 75 years and set

around a nice swimming pool. However, the highlight for

me was quite late in the party when Robin’s parents (in their

60s) and many others gazed with astonishment as Roy and

our lab’s lead technician, Edith Zeller opted to disrobe for a

refreshing swim. As for the October 2, 1983 wedding,

Robin’s parents hosted an incredible party, which Roy

seemed to enjoy (Fig. 1). Legend has it that he ate a fish

from the bowl.

‘The retardation of aging and disease by dietary

restriction’. Although I cannot recall the precise year,

around 1980 Roy came up with another great idea: to write a

book which comprehensively and critically discusses DR

(now a growing area of inquiry). It struck me as a huge but

important project to pursue. I do recall being concerned that

writing a book at such an early stage in one’s career is not

the normal career path (as it can only lower the number of

peer-reviewed research reports one can produce). Over the

next five years we had periods of time where progress was

made but ‘the book’ was always a secondary project.

However, this situation changed in the mid-1980s and a

concerted effort was made to complete this book.

In 1987, motivated by the birth of my daughter Erica and

the lack of a tenure-track position at UCLA, my family

relocated to Bethesda, MD so that I could pursue an

opportunity at the National Institute on Aging (NIA) where

the book was completed. In that regard, I acknowledge Evan

Hadley, my colleague/supervisor at NIA, for allowing me to

complete the book. Writing this book (Weindruch and

Walford, 1988) with Roy is a highlight of my career.

To conclude. Roy Walford is among the most gifted

individuals whom I have met. He is a unique individual

from multiple perspectives. This statement is supported by

his decision to become a Biospherian (Fig. 2). I am

privileged to have been his student and he remains my

collaborator (Barger et al., 2003) and friend.

References

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by caloric restriction: its significance in the transgenic era. Exp.

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Boveris, A., Chance, B., 1973. The mitochondrial generation of hydrogen

peroxide: general properties and effect of hyperbaric oxygen. Biochem.

J. 134, 707–716.

Lee, C.K., Allison, D.B., Brand, J., Weindruch, R., Prolla, T.A., 2002.

Transcriptional profiles associated with aging and middle age-onset

caloric restriction in mouse hearts. Proc. Natl Acad. Sci. USA 99,

14988–14993.

Nohl, H., Hegner, D., 1978. Do mitochondria produce oxygen radicals in

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