E-Letter responses to:

review: Caleb E. Finch and Eileen M. Crimmins Inflammatory Exposure and Historical Changes in Human Life-Spans Science 2004; 305: 1736-1739 [Abstract] [Full text] [PDF]

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Published E-Letter responses:

Secular Decreases, Human Life-Spans, Gender Differences and Month-of-Birth

Piet Hein A.L.M. Jongbloet   (4 January 2005)

Worms, Weather, Early-Age Inflammation, and Longevity

Vladimir N Melnikov, Lawrence E Frisch, Northeastern Ohio Universities College of Medicine, Youngstown, OH, U.S.A.   (24 November 2004)

Offspring Number and Morbidity

Susanne Huber, Martin Fieder (Dept Anthropology, Univ Vienna)   (22 October 2004)

Early-life and late-life morbidity

John J Harding   (22 October 2004)

Early-Life Exposure, Season of Birth and Gender Differences in Human Life Span

Leonid A Gavrilov, Ph.D., Leonid A. Gavrilov, Natalia S. Gavrilova   (6 October 2004)

Secular Decreases, Human Life-Spans, Gender Differences and Month-of-Birth 4 January 2005
Piet Hein A.L.M. Jongbloet, Paediatrician Dept. of Epidemiology and Biostatistics Respond to this E-Letter: Re: Secular Decreases, Human Life-Spans, Gender Differences and Month-of-Birth	Finch and Crimmins (1) document that cohorts of individuals with lower young-age mortality also have lower mortality at any given age later in life. They hypothesize that chronic inflammatory mechanisms drive much of the influence of early-life infections on later morbidity. Infections in early life and chronic diseases with inherent mortality, however, do not need to be causally related and are not isolated from the total spectrum of reproductive casualties, i.e., complications during pregnancy and parturition, chromosomal aberrations, congenital developmental defects, perinatal mortality, and most intriguing, sex ratio at birth. They all experience collateral secular decreases and, therefore, early- life infections cannot explain these cohort effects (2). We have argued that this parallelism is caused by reduction of conceptopathology due to preovulatory and postovulatory overripeness ovopathy (3), whose teratological effect has been established in animals (4). The perennial dwindling rate of pathological conceptions as a correlate to increasing socioeconomic development explains both the secular increase of the sex ratio running parallel with that of male- biased congenital defects, perinatal mortality, and morbidity (3). Infant morbidity and shortened life-span are also characterized by month-of-birth (5), which accounts for the same spectrum of reproductive casualties. These casualties again are related to an atavistic relict of seasonally bound "ovulatory" (spring and autumn) and "anovulatory" seasons (winter and summer). Fertilization of inappropriately matured oocytes during the inherent transitional stages are presumed to ensue excesses of male-biased pathological conceptuses in specific months, ill-implantation and loss during pregnancy, parturition, and preterm mortality (6). This effect has been documented in Down’s syndrome, anencephaly, perinatal mortality, diabetes mellitus, type 1, menstruation and eating disorders, schizophrenia, etc. [see (3, 6, 7)]. This effect in breast cancer incidence and shortened life-span (7) is well in line with this concept. In addition, the same casualties occur more after conceptions during other transitional stages of reproductive life, e.g., postmenarche, premenopause, postparturition, etc. In contrast, fertilization of optimally matured oocytes which coincide with the prime time of the "ovulatory seasons," is characterized by gender equity and full expression of the genetic potential of the gametes, and, thus, optimal birth weight, length, stature, eminence, and longevity (7). That means optimal vitality up to old age. Overall, inflammation during early life cannot be the major cause of early mortality resulting from chronic conditions in later age. Both casualties are rather consequence of ovopathy due to non-optimal maturation and fertilization of the oocyte. References 1. C. E. Finch, E. M. Crimmins, Science 305, 136 (2004). 2. T. Vartiainen, L. Kartovaara, J. Tuomisto, Environm. Perspect. 107, 813 (1999). 3. P. H. Jongbloet, G.A. Zielhuis, H.M.M. Groenewoud, P. C. M. Pasker-de Jong, J. Environm. Perspect. 109, 749 (2001). 4. K. Mikamo, Cytogenetics 7, 212 (1968). 5. G. Doblhammer, J.W. Vaupel, Proc. Natl. Acad. Sci. U.S.A. 98, 2934 (2001). 6. P. H. Jongbloet, Hum. Reprod. 19, 769 (2004). 7. P. H. Jongbloet, Coll. Antropol., 16, 99 (1992). 8. V. N. Melnikov, Epidemiology 15, 645 (2004). Piet Hein Jongbloet Ph.D., Paediatrician, Dept. of Epidemiology and Biostatistics Radboud University Nijmegen Medical Centre PO Box 9101 6500 Nijmegen The Netherlands E-MAIL: p.jongbloet@epib.umcn.nl
Worms, Weather, Early-Age Inflammation, and Longevity 24 November 2004
Vladimir N Melnikov, Human Biologist Siberian Independent Institute, Novosibirsk, Russia, Lawrence E Frisch, Northeastern Ohio Universities College of Medicine, Youngstown, OH, U.S.A. Respond to this E-Letter: Re: Worms, Weather, Early-Age Inflammation, and Longevity	Finch and Crimmins (1) offer an hypothesis that decreased early “inflammatory exposure” explains two centuries of falling cohort mortality. A similar “hygiene” hypothesis explains recent rises in childhood asthma through increased TH2/TH1 ratios from fewer respiratory infections (2). Since TH1 associates with elevated C-reactive protein (CRP) (3), a shift toward TH2 might reduce coronary deaths, although coronary disease was historically not a dominant cause of death until recently. While the authors offer no evidence that childhood respiratory pathogen exposure has decreased, it is likely that the 19th century did see decreasing parasitic infestations from sanitary improvements. Since IL-10 levels are increased following helminth infestation (4), reduced helminth exposure would likely lower levels of this anti-inflammatory cytokine. Elevated IL-10 levels increase susceptibility to pneumococcal pneumonia (5), so IL-10 reduction from fewer worms might have lowered death rates in the pre-antibiotic era. Further secular cohort mortality decreases might have come from cardioprotective CRP declines. Finch and Crimmins (1) and correspondents (6) comment on the important but incompletely understood relationship of birth-month to longevity. Recent studies of lung cancer and cardiovascular death in Siberian men demonstrate highly disease-specific associations between birth month and age at death [significantly older age at death for March- born lung cancer decedents (7) and for autumn-born coronary decedents (8)]. A successful hypothesis needs to explain these disease-specific variations as well as sex-specific differences in the relationship between birth month and longevity (6,7). Doblhammer and Vaupel (9) seem to have provided evidence against the idea that early childhood respiratory mortality (predominantly affecting those born in autumn (10)) culls inherently unhealthy individuals leaving the hardy remainder with reduced mortality into old age. “Inflammatory exposure” and its “hygiene” cousin face many obstacles, but both raise important questions about the effect of immune modulation on chronic disease and longevity. References 1. C.E. Finch, E.M. Crimmins, Science 305, 1736 (2004). 2. K.G. Tantisira, S.T. Weiss, Respir. Res. 2, 324 (2001). 3. H. Yamashita, K. Shimada, E. Seki, H. Mokuno, H. Daida, Am. J. Cardiol. 91, 133 (2003). 4. J.A. Jackson, J.D. Turner, L. Rentoul, H. Faulkner, J.M. Behnke, M. Hoyle, R.K. Grencis, K.J. Else, J. Kamgno, J.E. Bradley, M. Boussinesq, Int. J. Parasitol. 34, 1237 (2004). 5. K.F. van der Sluijs, L.J. van Elden, M.Nijhuis, R. Schuurman, J.M. Pater, S. Florquin, M. Goldman, H.M. Jansen, R. Lutter, T. van der Poll, J. Immunol. 15, 7603 (2004). 6. L.A. Gavrilov, N.S. Gavrilova, J. Anti-Aging Med. 2, 365 (1999). 7. V.N. Melnikov, Epidemiology 15, 645 (2004). 8. V.N. Melnikov, Int. J. Circumpolar Health 62, 296 (2003). 9. G. Doblhammer, J.W. Vaupel, Proc. Natl. Acad. Sci. U.S.A. 98, 2934 (2001). 10. V.N. Melnikov, Proc. 9th Russian Nat. Congr. Lung Diseases, Abstract LXV.2 (1999). The English version is available at http://infoteka.nsk.ru/~oval
Offspring Number and Morbidity 22 October 2004
Susanne Huber, Biologist Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Martin Fieder (Dept Anthropology, Univ Vienna) Respond to this E-Letter: Re: Offspring Number and Morbidity	In their review, Finch and Crimmins (1) report strong associations between early-age mortality and subsequent mortality. One factor that might be important in this regard is offspring number because a potential decline in offspring number during the investigated time period might be related to a decrease in morbidity and mortality both during early age and old age. It is known that a decline in offspring number is associated with more extensive investment in each of the fewer children (2). And investing more extensively in fewer children probably comprises both improved health care during infancy, which reduces infection risk during early age (3), and higher education and thus improved standard of living during adulthood, which reduces morbidity in old age (4). References 1. C. E. Finch, E. M. Crimmings, Science 305, 1736 (2004). 2. G. S. Becker. Human Capital. (University of Chicago Press, Chicago, 1993). 3. M. Ali, M. Emch, F. Tofail, A. H. Baqui, Soc. Sci. Med. 52, 267 (2001). 4. M. Marmot. The Status Syndrome. How Social Standing Affects Our Health and Longevity. (Henry Holt and Company, New York, 2004).
Early-life and late-life morbidity 22 October 2004
John J Harding, Biochemist Nuffield Laboratory of Ophthalmology, University of Oxford, UK. Respond to this E-Letter: Re: Early-life and late-life morbidity	Finch and Crimmins (1) assemble convincing evidence that mortality in old age is related to infant mortality of the same cohort. They promote the fascinating notion that the inflammatory response to a variety of infectious diseases in infancy persists for decades and takes its toll at the other end of the life span. Part of the evidence cited for this is that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of late-life vascular events and Alzheimer’s disease. It should be noted that NSAIDs also appear to protect against cataract (2), colon cancer (3), and prostate cancer (4), all increasingly common late in life. Severe diarrhea is a major risk factor for cataract in third world countries where cataract prevalence is high, and diarrheal conditions early in life may lead to cataract in adults (5). In this scientific area, part of the explanantion has been that post-translational modification of proteins, especially long-lived proteins, provides a vulnerability that can manifest later in life as lens opacity (6). Proteins in most lens cells do not turn over and therefore can accumulate damage. In cataract, it is difficult to untangle the roles of post-translational modification of proteins and nutritional defects, and diarrhea can lead to both. Finch and Crimmins point out that the inflammatory and nutritional hypotheses are complementary in linking early and late life morbidity. In addition, pathways through post-translational modification and conformational change to proteins could also be complementary to these. Age-related diseases are truly multifactorial. References 1. C. E. Finch, E. M. Crimmins. Science 305, 1736 (2004). 2. J. J. Harding. Drugs and Ageing 18, 473 (2001). 3. P. A. Janne, R. J. Mayer. New Eng. J. Med. 342, 1960 (2000). 4. J. E. Nelson, R. E. Harris. Oncol. Rep. 7, 169 (2000). 5. J. J. Harding. Cataract: Biochemistry, Epidemiology and Pharmacology (Chapman and Hall, London, 1991). 6. J. J. Harding. Ageing Res. Rev. 1, 465 (2002).
Early-Life Exposure, Season of Birth and Gender Differences in Human Life Span 6 October 2004
Leonid A Gavrilov, Ph.D., Scientist, Center on Aging, NORC/University of Chicago, Leonid A. Gavrilov, Natalia S. Gavrilova Respond to this E-Letter: Re: Early-Life Exposure, Season of Birth and Gender Differences in Human Life Span	A review by Finch and Crimmins (1) reinforces an earlier suggestion that "many diseases and disabilities of older age have their roots in previous exposures to infectious agents in early life," by mechanism of "inflammation, which is common in many infectious diseases" [(2), p. 260]. The review appropriately discusses the effects of the season of birth on human longevity, although that particular cited publication was later disputed on methodological grounds (3,4). Fortunately, the season-of-birth effect on human longevity was demonstrated in other studies (5,6) as well, bringing further attention to seasonal variation in disease load and its long-term consequences. New interesting developments of the "inflammatory" hypothesis may come from analysis of gender differences. It is known that an increase in life expectancy at older ages is particularly strong among women (7, 8). Surprisingly, it is also women who demonstrate the strongest season-of- birth effect on adult lifespan (3, 4). Thus, the "inflammatory" hypothesis is now presented with an interesting task of explaining why women are particularly sensitive to early-life conditions. References 1. C. E. Finch, E. M. Crimmins, Science 305, 1736 (2004). 2. V. Glaser, J. Anti-Aging Med. 5, 255 (2002). 3. N. S. Gavrilova, L. A. Gavrilov, G. N. Evdokushkina, V.G. Semyonova, Annales de Demographie Historique 2, 177 (2003). 4. L. A. Gavrilov, N. S. Gavrilova, "Early-life factors modulating lifespan," in: Modulating Aging and Longevity, S.I.S. Rattan, Ed. (Kluwer Academic, Dordrecht, Netherlands, 2003). 5. L. A. Gavrilov, N. S. Gavrilova, J. Anti-Aging Med. 2, 365 (1999). 6. L. A. Gavrilov, N. S. Gavrilova, Ann. N.Y. Acad. Sci. 1019, 496 (2004). 7. L. A. Gavrilov, V. N. Nosov, Age 8, 93 (1985). 8. L. A. Gavrilov, N. S. Gavrilova, The Biology of Life Span: A Quantitative Approach (Harwood Academic, New York, 1991).