- Email: [email protected]
Dining with Roy
Experimental Gerontology 39 (2004) 893–894 www.elsevier.com/locate/expgero
Discussion
Dining with Roy Caleb E. Finch* Ethel Percy Andrus Gerontology Center and Department of Biological sciences University of Southern California, Los Angeles, CA 90089-0191, USA
Keywords: Walford; diet restriction; fish; Mhc; aging
When Roy entered Biosphere 2 in 1991 at age 67, he was in superb condition and rippled with lean muscle from power lifting at Gold’s Gym. No evident harm from his minimalist diet! At a hilarious send-off dinner party in LA, Roy showed his top form in every respect. But some 16 months later, Roy sounded strange. One evening with friends, I had been describing Roy’s life in the Biosphere and thought it would be fun for all to exchange a few words, and so called his private phone. It was disturbing to hear his usually resonant voice pipe out of the Biosphere as flat and halting. Soon after, Roy recognized the problem of oxygen deficits, when he realized that he no longer could do simple arithmetic. He called for emergency input of oxygen and his usual voice and cognition recovered. Although the plant life in Biosphere2 produced as much oxygen as predicted, there was the unanticipated oxygen loss by its adsorption into the Biosphere’s huge concrete surfaces (Walford et al., 1996). At that time the pO2 was equivalent to 14,000 feet, but the pCO and pCO2 were closer to sea level. We will never know if the strange atmosphere was a factor in Roy’s amyotrophic lateral sclerosis (ALS) which developed slowly over the next decade. This abnormal ratio of metabolic gases could perturb free radicle production, leading to neurological damage. Another possibility is neurotoxic effects from the organic pesticides and pollutants (DDE and PCB), which were liberated as body fat dwindled slowly during the spartan diet and exercise regimen (Walford et al., 1999). More than ten fascinating papers describe the physiology and biology of this unique experience. Except for the atmospheric perturbation, the other engineered aspects of the Biosphere ecology held up well and are yielding a wealth of data which NASA considers important for designing future space travel. I agree with Roy’s belief that robotics and technical advances in space travel should never replace direct human observations. * Tel.: þ1-213-740-1756; fax: þ 1-213-740-0853. E-mail address: [email protected] (C.E. Finch). 0531-5565/$ - see front matter q 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2004.03.006
Before and after Biosphere, we often met at fine restaurants in Los Angeles and abroad. At our dinners Roy always relaxed his frugal discipline. How statistically unlikely, I would joke, that our dinners always fell on his alternate days of feeding. Roy said that at many other dinners he would keep to his minimalist diet, while others around him chomped away and looked at him as if he were “being naughty”. We observed no limits to fine food and wine, nor to topics of conversation. These were some of the greatest dialogues in my life. It has taken me decades of close contact to appreciate the reach of Roy’s intellectual and geographic travels. I soon came to expect surprises at every turn in this free spirit of so many domains. Roy had a wonderful education of highlevel quantitative skills from his physics major at Caltech, plus his uncommonly deep understanding of how the human organism works from his clinical days. Roy and I first met when I was a graduate student in New York in 1968. His was clearly an unusual mind with a remarkable breadth of curiosity and drive to challenge and change the world. We both saw the great potential in building the field of biogerontology. We also shared a revulsion of the US war in Asia and anger at the politics and society that allowed it. We also shared interests in performing arts, literature, and adventures. Roy’s classic book “The Immunological Theory of Aging” (1969) came out the same year I finished my PhD. Although I didn’t buy all of the arguments, this book is pioneering in its treatment of aging as an integrative process across organ systems which I felt was compatible with my emerging hypothesis of aging is a neuroendocrine-driven process (Finch, 1973). In scanning through it again after these 35 years, I find his book even more amazing and realize I didn’t know enough to fully appreciate it. The last sentence is “Long live freedom”, which epitomizes his daring integrative arguments. Nor did I know until later that Roy was a member of the crucial early Human Lymphocyte Antigen (HLA)
894
C.E. Finch / Experimental Gerontology 39 (2004) 893–894
Workshops with Jean Dausset, which were charting the basis for the present huge field of immunogenetics. Roy had already written an important early monograph, “Leukocyte antigens and antibodies” (1960). When we met, Roy was beginning to look at the immune system in calorically restricted mice (Walford et al., 1973). Not long after, I moved to Los Angeles and our paths have crossed increasingly ever since. Another shared interest in our early conversations was comparative gerontology. I had become fascinated in writing my thesis with the diverse life histories of fish (Finch, 1969). Roy added importantly to this small literature by the first life span study of one of the world’s smallest fish, the gobie (Pandaka pygmea) (, 11 mm and 20 mg wet weight), which he brought back from the Philippines for comparison with the annual fish Cynolebias and several other gobies (Liu and Walford, 1970). All fish lived at least a year, with no relationship to body size, contrary to dogma. Moreover, Cynolebias grew faster at cold temperatures, contrary to the simple rate of living hypothesis (Liu et al., 1975). This work added importantly to Comfort’s studies of the gobies as a model for aging and started me to collect further fish examples that eventually were discussed in my first book, “Longevity, Senescence, and the Genome” (Finch, 1990). Since then, another even smaller gobie has come to light, Trimmatom nanus (8 mm), (Nelson, 1994; Winterbottom and Emery, 1981). Roy and I really grew involved, when he invited my participation in an NIA program grant on the Major Histocompatibility Complex (Mhc) gene system in aging. The germ of these ideas was clearly articulated in Roy’s 1969 book. This program grant included Steve Spindler, Toshiko Immamura, and George Smith. These research discussions during the five years 1983-1988 were of great value to me and lead to our own findings the Mhc haplotypes influence the estrous cycle length in young mice (Lerner et al., 1988; Lerner and Finch, 1991) and also aspects of reproductive aging (Lerner et al., 1992). The evolutionarily deep integration of immune and neuroendocrine functions within the large Mhc locus gives a basis for developing the concept of a ‘life history gene complex’ (Finch and Rose, 1995). During the early ‘70’s Roy began his major work in caloric restriction (Walford et al., 1973), which greatly extended the earlier work of Clive McCay and Morris Ross, and set the stage for many important investigators. A series of major papers with Rich Weindruch showed the benefits to aging could be obtained even when begun later and were clearly not due to developmental arrest. My lab was persuaded to examine the brains of calorically restricted mice. Suffice it to say, caloric restriction has become a major paradigm in the neurobiology of aging. We discovered that caloric restriction attenuates glial activation during aging (Nichols et al., 1995) and most recently that caloric restriction slows the accumulation of amyloid in transgenic models of familial Alzheimer disease (Patel et al., submitted).
Roy invited me to a Hollywood party in honor of his book with his daughter Lisa Walford, “Hundred Twenty Year Diet” (1986). What a freak-show! Roy introduced me to his pal, the former Harvard psychologist Timothy O’Leary, whose eyes were dilated and seemed unable to hold a conversation, whilst others around were talking too fast to converse. Roy’s lives in so many diverse parts of the human labyrinth are hinted at in Lisa’s pithy biography. While continuing to run an active lab and recruit new talent into aging, Roy also also maintained his very full life outside of science. I envied his discipline of leaving the lab at 5 p.m. to take advanced courses in multimedia technology. Even when the grip of ALS began to close in on him, Roy continued to expand his scientific and humanistic spheres. Until 6 months ago, Roy was still able to share a take-out meal in his Venice loft, but at our last meeting in November he asked me to eat first. Still, we struck some sparks, with old tales retold and fantasies of times to come. Writing this is unbearably sad. As Roy will always say, “Long live freedom!”.
References Finch, C.E., 1969. Cellular Activities During Aging in Mammals. PhD Dissertation, The Rockefeller University. MSS Information Corporation, New York, NY. Finch, C.E., 1973. Catecholamine metabolism in the brains of ageing male mice. Brain Res. 52, 261–276. Finch, C.E., 1990. Longevity, Senescence, and the Genome, University of Chicago Press, Chicago, IL. Finch, C.E., Rose, M.R., 1995. Hormones and the physiological architecture of life history evolution. Q. Rev. Biol. 70, 1– 52. Lerner, S.P., Anderson, C.P., Finch, C.E., 1988. Genotypic influences on female reproductive senescence in mice. Biol. Repro. 38, 1035–1044. Lerner, S.P., Finch, C.E., 1991. The major histocompatibility complex and reproductive functions. Endocrine Rev. 12, 78–90. Liu, R.K., Walford, R.L., 1970. Observations on the lifespans of several species of annual fishes and of the world’s smallest fishes. Exp. Gerontol. 5, 241 –246. Liu, R.K., Leung, B.E., Walford, R.L., 1975. Effect of temperature-transfer on growth of laboratory populations of a South American annual fish Cynolebias bellottii. Growth 39, 337–343. Nelson, J.S., 1994. Fishes of the world, third ed, Wiley, New York, NY. Nichols, N.R., Finch, C.E., Nelson, J.F., 1995. Food restriction delays the age-related increases of GFAP mRNA in rat hypothalamus. Neurobiol. Ageing 16, 105– 110. Walford, R.L., Liu, R.K., Gerbase-Delima, M., Mathies, M., Smith, G.S., 1973. Longterm dietary restriction and immune function in mice: response to sheep red blood cells and to mitogenic agents. Mech. Ageing Dev. 2, 447–454. Walford, R.L., Bechtel, R., MacCallum, T., Paglia, D.E., Weber, L.J., 1996. Biospheric medicine as viewed from the two-year first closure of Biosphere 2. Aviat. Space Environ. Med. 67, 609–617. Walford, R.L., Mock, D., MacCallum, T., Laseter, J.L., 1999. Physiologic changes in humans subjected to severe, selective calorie restriction for two years in Biosphere 2: health, aging, and toxicological perspectives. Toxicol. Sci. 52, 61–65. Winterbottom, R., Emery, A.R., 1981. A new genus and two new species of gobiid fishes (Perciformes) from the Chagos Archipelago, central Indian Ocean. Environ. Biol. Fishes 6, 139–149.
Discussion
Dining with Roy Caleb E. Finch* Ethel Percy Andrus Gerontology Center and Department of Biological sciences University of Southern California, Los Angeles, CA 90089-0191, USA
Keywords: Walford; diet restriction; fish; Mhc; aging
When Roy entered Biosphere 2 in 1991 at age 67, he was in superb condition and rippled with lean muscle from power lifting at Gold’s Gym. No evident harm from his minimalist diet! At a hilarious send-off dinner party in LA, Roy showed his top form in every respect. But some 16 months later, Roy sounded strange. One evening with friends, I had been describing Roy’s life in the Biosphere and thought it would be fun for all to exchange a few words, and so called his private phone. It was disturbing to hear his usually resonant voice pipe out of the Biosphere as flat and halting. Soon after, Roy recognized the problem of oxygen deficits, when he realized that he no longer could do simple arithmetic. He called for emergency input of oxygen and his usual voice and cognition recovered. Although the plant life in Biosphere2 produced as much oxygen as predicted, there was the unanticipated oxygen loss by its adsorption into the Biosphere’s huge concrete surfaces (Walford et al., 1996). At that time the pO2 was equivalent to 14,000 feet, but the pCO and pCO2 were closer to sea level. We will never know if the strange atmosphere was a factor in Roy’s amyotrophic lateral sclerosis (ALS) which developed slowly over the next decade. This abnormal ratio of metabolic gases could perturb free radicle production, leading to neurological damage. Another possibility is neurotoxic effects from the organic pesticides and pollutants (DDE and PCB), which were liberated as body fat dwindled slowly during the spartan diet and exercise regimen (Walford et al., 1999). More than ten fascinating papers describe the physiology and biology of this unique experience. Except for the atmospheric perturbation, the other engineered aspects of the Biosphere ecology held up well and are yielding a wealth of data which NASA considers important for designing future space travel. I agree with Roy’s belief that robotics and technical advances in space travel should never replace direct human observations. * Tel.: þ1-213-740-1756; fax: þ 1-213-740-0853. E-mail address: [email protected] (C.E. Finch). 0531-5565/$ - see front matter q 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.exger.2004.03.006
Before and after Biosphere, we often met at fine restaurants in Los Angeles and abroad. At our dinners Roy always relaxed his frugal discipline. How statistically unlikely, I would joke, that our dinners always fell on his alternate days of feeding. Roy said that at many other dinners he would keep to his minimalist diet, while others around him chomped away and looked at him as if he were “being naughty”. We observed no limits to fine food and wine, nor to topics of conversation. These were some of the greatest dialogues in my life. It has taken me decades of close contact to appreciate the reach of Roy’s intellectual and geographic travels. I soon came to expect surprises at every turn in this free spirit of so many domains. Roy had a wonderful education of highlevel quantitative skills from his physics major at Caltech, plus his uncommonly deep understanding of how the human organism works from his clinical days. Roy and I first met when I was a graduate student in New York in 1968. His was clearly an unusual mind with a remarkable breadth of curiosity and drive to challenge and change the world. We both saw the great potential in building the field of biogerontology. We also shared a revulsion of the US war in Asia and anger at the politics and society that allowed it. We also shared interests in performing arts, literature, and adventures. Roy’s classic book “The Immunological Theory of Aging” (1969) came out the same year I finished my PhD. Although I didn’t buy all of the arguments, this book is pioneering in its treatment of aging as an integrative process across organ systems which I felt was compatible with my emerging hypothesis of aging is a neuroendocrine-driven process (Finch, 1973). In scanning through it again after these 35 years, I find his book even more amazing and realize I didn’t know enough to fully appreciate it. The last sentence is “Long live freedom”, which epitomizes his daring integrative arguments. Nor did I know until later that Roy was a member of the crucial early Human Lymphocyte Antigen (HLA)
894
C.E. Finch / Experimental Gerontology 39 (2004) 893–894
Workshops with Jean Dausset, which were charting the basis for the present huge field of immunogenetics. Roy had already written an important early monograph, “Leukocyte antigens and antibodies” (1960). When we met, Roy was beginning to look at the immune system in calorically restricted mice (Walford et al., 1973). Not long after, I moved to Los Angeles and our paths have crossed increasingly ever since. Another shared interest in our early conversations was comparative gerontology. I had become fascinated in writing my thesis with the diverse life histories of fish (Finch, 1969). Roy added importantly to this small literature by the first life span study of one of the world’s smallest fish, the gobie (Pandaka pygmea) (, 11 mm and 20 mg wet weight), which he brought back from the Philippines for comparison with the annual fish Cynolebias and several other gobies (Liu and Walford, 1970). All fish lived at least a year, with no relationship to body size, contrary to dogma. Moreover, Cynolebias grew faster at cold temperatures, contrary to the simple rate of living hypothesis (Liu et al., 1975). This work added importantly to Comfort’s studies of the gobies as a model for aging and started me to collect further fish examples that eventually were discussed in my first book, “Longevity, Senescence, and the Genome” (Finch, 1990). Since then, another even smaller gobie has come to light, Trimmatom nanus (8 mm), (Nelson, 1994; Winterbottom and Emery, 1981). Roy and I really grew involved, when he invited my participation in an NIA program grant on the Major Histocompatibility Complex (Mhc) gene system in aging. The germ of these ideas was clearly articulated in Roy’s 1969 book. This program grant included Steve Spindler, Toshiko Immamura, and George Smith. These research discussions during the five years 1983-1988 were of great value to me and lead to our own findings the Mhc haplotypes influence the estrous cycle length in young mice (Lerner et al., 1988; Lerner and Finch, 1991) and also aspects of reproductive aging (Lerner et al., 1992). The evolutionarily deep integration of immune and neuroendocrine functions within the large Mhc locus gives a basis for developing the concept of a ‘life history gene complex’ (Finch and Rose, 1995). During the early ‘70’s Roy began his major work in caloric restriction (Walford et al., 1973), which greatly extended the earlier work of Clive McCay and Morris Ross, and set the stage for many important investigators. A series of major papers with Rich Weindruch showed the benefits to aging could be obtained even when begun later and were clearly not due to developmental arrest. My lab was persuaded to examine the brains of calorically restricted mice. Suffice it to say, caloric restriction has become a major paradigm in the neurobiology of aging. We discovered that caloric restriction attenuates glial activation during aging (Nichols et al., 1995) and most recently that caloric restriction slows the accumulation of amyloid in transgenic models of familial Alzheimer disease (Patel et al., submitted).
Roy invited me to a Hollywood party in honor of his book with his daughter Lisa Walford, “Hundred Twenty Year Diet” (1986). What a freak-show! Roy introduced me to his pal, the former Harvard psychologist Timothy O’Leary, whose eyes were dilated and seemed unable to hold a conversation, whilst others around were talking too fast to converse. Roy’s lives in so many diverse parts of the human labyrinth are hinted at in Lisa’s pithy biography. While continuing to run an active lab and recruit new talent into aging, Roy also also maintained his very full life outside of science. I envied his discipline of leaving the lab at 5 p.m. to take advanced courses in multimedia technology. Even when the grip of ALS began to close in on him, Roy continued to expand his scientific and humanistic spheres. Until 6 months ago, Roy was still able to share a take-out meal in his Venice loft, but at our last meeting in November he asked me to eat first. Still, we struck some sparks, with old tales retold and fantasies of times to come. Writing this is unbearably sad. As Roy will always say, “Long live freedom!”.
References Finch, C.E., 1969. Cellular Activities During Aging in Mammals. PhD Dissertation, The Rockefeller University. MSS Information Corporation, New York, NY. Finch, C.E., 1973. Catecholamine metabolism in the brains of ageing male mice. Brain Res. 52, 261–276. Finch, C.E., 1990. Longevity, Senescence, and the Genome, University of Chicago Press, Chicago, IL. Finch, C.E., Rose, M.R., 1995. Hormones and the physiological architecture of life history evolution. Q. Rev. Biol. 70, 1– 52. Lerner, S.P., Anderson, C.P., Finch, C.E., 1988. Genotypic influences on female reproductive senescence in mice. Biol. Repro. 38, 1035–1044. Lerner, S.P., Finch, C.E., 1991. The major histocompatibility complex and reproductive functions. Endocrine Rev. 12, 78–90. Liu, R.K., Walford, R.L., 1970. Observations on the lifespans of several species of annual fishes and of the world’s smallest fishes. Exp. Gerontol. 5, 241 –246. Liu, R.K., Leung, B.E., Walford, R.L., 1975. Effect of temperature-transfer on growth of laboratory populations of a South American annual fish Cynolebias bellottii. Growth 39, 337–343. Nelson, J.S., 1994. Fishes of the world, third ed, Wiley, New York, NY. Nichols, N.R., Finch, C.E., Nelson, J.F., 1995. Food restriction delays the age-related increases of GFAP mRNA in rat hypothalamus. Neurobiol. Ageing 16, 105– 110. Walford, R.L., Liu, R.K., Gerbase-Delima, M., Mathies, M., Smith, G.S., 1973. Longterm dietary restriction and immune function in mice: response to sheep red blood cells and to mitogenic agents. Mech. Ageing Dev. 2, 447–454. Walford, R.L., Bechtel, R., MacCallum, T., Paglia, D.E., Weber, L.J., 1996. Biospheric medicine as viewed from the two-year first closure of Biosphere 2. Aviat. Space Environ. Med. 67, 609–617. Walford, R.L., Mock, D., MacCallum, T., Laseter, J.L., 1999. Physiologic changes in humans subjected to severe, selective calorie restriction for two years in Biosphere 2: health, aging, and toxicological perspectives. Toxicol. Sci. 52, 61–65. Winterbottom, R., Emery, A.R., 1981. A new genus and two new species of gobiid fishes (Perciformes) from the Chagos Archipelago, central Indian Ocean. Environ. Biol. Fishes 6, 139–149.