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Gerontology by Bruce Carnes

Scientific American, 1993

Science of Aging Knowledge Environment, 2002

Scientific American, 2001

Journal of Aging and Health, 1991

This article demonstrates and explains why future declines in mortality will have a diminishing e... more This article demonstrates and explains why future declines in mortality will have a diminishing effect on the metric of life expectancy but a large impact on the size of future elderly cohorts. Additionally, the article addresses a hypothesis in which it is argued that morbidity and disability will decline and become compressed into a shorter duration of time before death. Although studies have demonstrated that declining mortality can lead to worsening health, what is missing from the literature is a formal mechanistic hypothesis that describes why this phenomenon takes place. Two primary mechanisms are identified. One is based on arguments in which medical technology is identified to improve the survival of those with disabling conditions; the other is that declining mortality from fatal diseases leads to a shift in the distribution of causes of disability from fatal to nonfatal diseases of aging. Procedures for testing this hypothesis are discussed.

New England Journal of Medicine, 2005

Mechanisms of Ageing and Development, 2008

Biodemography by Bruce Carnes

Population and Development Review, 2007

Biodemography and Social Biology, 2002

Biodemography of human longevity is an emerging interdisciplinary field of sociobiological resear... more Biodemography of human longevity is an emerging interdisciplinary field of sociobiological research with deep historical roots. Two research questions are examined in this article: (1) What evidence is there for the familial transmission of human longevity?, and (2) what are the effects of parental age at reproduction on offspring longevity, and in particular, are there long‐term adverse health consequences associated with the trend toward delayed reproduction? The ability of scientists to conduct biodemographic studies depends not only on merging theoretical and methodological elements from the biological and demographic/actuarial sciences, but unique sources of data and statistical methods must also be developed. In this article we describe how genealogical data have been used for over a century to explore basic questions about human longevity, and how similar kinds of data now being developed are driving the formation of new testable research hypotheses in the field of biodemography.

Science, 1990

Estimates of the upper limits to human longevity have important policy implications that directly... more Estimates of the upper limits to human longevity have important policy implications that directly affect forecasts of life expectancy, active life expectancy, population aging, and social and medical programs tied to the size and health status of the elderly population. In the past, investigators have based speculations about the upper limits of human longevity on observations of past trends in mortality. Here the estimate of the upper bound is based on hypothesized reductions in current mortality rates necessary to achieve a life expectancy at birth from 80 to 120 years and an expectation of life at age 50 from 30 to 70 years. With the use of conditional probabilities of death from complete life tables for the United States, reductions in mortality required to achieve extreme longevity (that is, 80 to 120 years) were compared with those resulting from hypothetical cures for all cardiovascular diseases, ischemic heart disease, diabetes, and cancer. Results indicate that in order for life expectancy at birth to increase from present levels to what has been referred to as the average biological limit to life (age 85), mortality rates from all causes of death would need to decline at all ages by 55%, and at ages 50 and over by 60%. Given that hypothetical cures for major degenerative diseases would reduce overall mortality by 75%, it seems highly unlikely that life expectancy at birth will exceed the age of 85.

Scientific American, 1993

Science of Aging Knowledge Environment, 2002

Scientific American, 2001

Journal of Aging and Health, 1991

New England Journal of Medicine, 2005

Mechanisms of Ageing and Development, 2008

Population and Development Review, 2007

Biodemography and Social Biology, 2002

Science, 1990

Experimental Gerontology, 1997

Biogerontology, 2003

Projections of duration of life for humansbased on mathematical models have led someresearchers t... more Projections of duration of life for humansbased on mathematical models have led someresearchers to claim that there is no lowerlimit to death rates or upper limit to lifeexpectancy, and that a life expectancy of 100will be achieved in the 21st century. Toassess the biological plausibility of theseclaims, we examined temporal aspects ofbiological phenomena in three mammalianspecies. Our examination revealed that: (1)physiological declines associated withreproduction consistently occur at ages thatare less than one-third of the median age atdeath, (2) physiological parameters associatedwith aging in humans lose eighty percent oftheir functional capacity by age 80, and (3)young versus old individuals can bedistinguished by the pathologies detected atdeath. The biological evidence suggests thatorganisms operate under warranty periods thatlimit the duration of life of individuals andthe life expectancy of populations. We usethese findings to discuss the issue of limitsto the duration of life and the validity ofmathematical models used to forecast humanlongevity.

Biogerontology, 2006

The reasons for classifying causes of death into aggregate groups are discussed and the impact of... more The reasons for classifying causes of death into aggregate groups are discussed and the impact of mortality partitions on analyses of mortality is described. Special emphasis is given to a mortality partition that distinguishes between intrinsic causes of death that arise primarily from the failure of biological processes that originate within an organism, and extrinsic causes of death that are primarily imposed on the organism by outside forces. Examples involving mortality data for mice, dogs, and humans are used to illustrate how this mortality partition infuses biological reasoning into mathematical models used to analyze and predict senescent-determined mortality, enhances the information content of the mortality schedules generated from these models, improves mortality comparisons between populations within species separated by time or geographic location, and provides a logical pathology endpoint for making interspecies comparisons of mortality. By bridging biology and the statistics of mortality, a mortality partition based on intrinsic and extrinsic causes of death provides both structure and direction for research on senescent-determined mortality.

Population and Development Review, 2002

The life span of individuals and the life expectancy of the populations they comprise have always... more The life span of individuals and the life expectancy of the populations they comprise have always been topics of interest to scientists and the lay population. In modern times, forecasts of life span and life expectancy have become particularly important public policy issues because of their influence on the future solvency of age-entitlement programs. The authors present a brief discussion of the origin of the notion of life span, discuss its relevance and importance in light of recent developments in the emerging field of the biodemography of aging, and explore the theoretical and biological forces that influence the duration of life of sexually reproducing species.

Emerging Themes in Epidemiology, 2005

Experimental Gerontology, 2001

Leukemia Research, 1989

Male beagles chronically exposed to low daily doses of 60Co gamma rays (7.5 cGy/22h/day) show one... more Male beagles chronically exposed to low daily doses of 60Co gamma rays (7.5 cGy/22h/day) show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival (-S-AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders (+R-MPD group); or (3) high radioresistance with other nonMPD syndromes (+R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model, thus defining the (a) initial suppressive and (b) subsequent recovery phases for the subgroups. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked -S-AA much greater than +R-MPD greater than +R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked +R-MPD greater than +R-nonMPD much much greater than -S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the +R-nonMPD subgroup consistently exhibited stronger responses than the +R-MPD subgroup. These results tend to support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression.

Photochemistry and Photobiology, 1987

Abstract— An action spectrum for the immediate induction in DNA of single-strand breaks (SSBs, fr... more Abstract— An action spectrum for the immediate induction in DNA of single-strand breaks (SSBs, frank breaks plus alkali-labile sites) in human P3 teratoma cells in culture by monochromatic 254-, 270-, 290-, 313-, 334-, 365-, and 405-nm radiation is described. The cells were held at +0.5d̀C during irradiation and were Iysed immediately for alkaline sedimentation analysis following the irradiation treatments. Linear fluence responses were observed over the fluence ranges studied for all energies. Irradiation of the cells in a D2O environment (compared with the normal H2O environment) did not alter the rate of induction of SSBs by 290-nm radiation, whereas the D2O environment enhanced the induction of SSBs by 365- and 405-nm irradiation. Analysis of the relative efficiencies for the induction of SSBs, corrected for quantum efficiency and cellular shielding, revealed a spectrum that coincided closely with nucleic acid absorption below 313 nm. At longer wavelengths, the plot of relative efficiency vs. wavelength contained a minor shoulder in the same wavelength region as that observed in a previously obtained action spectrum for stationary phase Bacillus subtilis cells. Far-UV radiation induced few breaks relative to pyrimidine dimers, whereas in the near-UV region of radiation, SSBs account for a significant proportion of the lesions relative to dimers, with a maximum number of SSBs per lethal event occurring at 365-nm radiation.

Cancer Letters, 1987

Relative frequencies of diethylnitrosamine (DEN)-initiated foci of altered hepatocytes appearing ... more Relative frequencies of diethylnitrosamine (DEN)-initiated foci of altered hepatocytes appearing in response to promotion by either dietary phenobarbital or a topically applied coal-derived organic mixture (CDM) were investigated in male and female rats. The focus population was examined for two histochemical markers, elevated gamma-glutamyl transpeptidase [GG(+)] and iron exclusion [FE(-)], giving rise to 3 detectable focus phenotypes, i.e., GG(+) foci, FE(-) foci, and GG(+)/(FE(-) foci. Frequencies of the 3 phenotypes were quantitated through the use of serial frozen sectioning and computer-assisted image analysis. In agreement with our prior observations, cutaneous exposure to CDM or dietary phenobarbital promoted the expression of DEN-initiated foci. However, the current data showed that this promoting effect of CDM occurred only in females and was restricted to foci with the GG(+)/FE(-) phenotype. Dietary phenobarbital, on the other hand, promoted both the GG(+) and GG(+)/FE(-) phenotypes and was effective in both males and females, although a sex-related differential in the promoting efficiency of phenobarbital was also observed. The pronounced heterogeneity in the responses of the 3 focus phenotypes suggests that each phenotype is the consequence of a specific type of genomic alteration with a specific capacity to undergo phenotypic expression in response to a given promoting stimulus.

Carcinogenesis, 1987

To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (D... more To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (DEN) on the induction of histochemically detectable altered hepatocyte foci and hepatic tumors, we assessed the yields of these lesions in the livers of 150-day-old rats that had been treated neonatally with a single dose of gamma radiation (75 rad, whole body) and i.p.-injected DEN (0.15 mumol/g body wt), either separately or in combination. The combined treatments involved the administration of the two stimuli in both possible sequences, with the interval between treatments set at 1 h. The focus population was examined for two histochemical markers (elevated gamma-glutamyl transpeptidase [GGT(+)] and iron exclusion [FE(-)], giving rise to three detectable focus phenotypes, i.e. GGT(+) foci, FE(-) foci, and GGT(+), FE(-) foci. Frequencies of the three phenotypes were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. GGT(+) focus induction was synergistically enhanced by the combined treatment irrespective of the order in which the two stimuli were administered; the remaining two phenotypes did not show such enhancement. The magnitude of the GGT(+) focus response was significantly greater when the treatment sequence was gamma----DEN as opposed to DEN----gamma. Tumor yields in rats receiving combined gamma--DEN treatment were similar to those in rats receiving the DEN alone, irrespective of the gamma--DEN treatment sequence. These results suggest that phenotypically distinguishable lesions, including foci with different histochemical marker patterns and tumors, originate from specific types of damage at different genetic loci and are developmentally independent; and the expression of the GGT(+) marker per se in altered hepatocyte foci is not a reliable index of incipient hepatic neoplasia.

Carcinogenesis, 1986

Relationships between phenotypic and growth characteristics of carcinogen-induced altered hepatoc... more Relationships between phenotypic and growth characteristics of carcinogen-induced altered hepatocyte foci were investigated. Male and female rats were given a single i.p. injection of carcinogen (diethylnitrosamine or benzo[a]pyrene) within 1 day after birth and were exposed to dietary promoter (phenobarbital) beginning at weaning. Groups of these rats were then killed at intervals, and their livers were examined for foci exhibiting various phenotypic markers through the use of serial frozen sectioning techniques, histochemical staining and computer-assisted image analysis. These procedures permitted the identification and sizing of foci with different specific phenotypes (identities of focus markers) within each phenotypic complexity level (number of markers per focus). The data suggest that foci growth rates differ with respect to specific focus phenotypes within complexity levels. This observation complements previous demonstrations of a direct relationship between foci growth rates and levels of phenotypic complexity and indicates that the observed diversity of focus phenotypes reflects true biological diversity within the focus population. Given the prior evidence for (i) the stability of focus phenotypes; (ii) the rapid emergence of phenotypically dissimilar foci following a single carcinogen treatment; and (iii) the production of foci by single initiation events, we suggest that each proliferatively and phenotypically distinct member of the focus population reflects the occurrence of a lesion at a unique genetic locus during initiation.