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Biomedical subjects

Kenneth G Manton

Publications and source records attributed to Kenneth G Manton.

16 recordsLinked to original sources
PubMed2006

Change in chronic disability from 1982 to 2004/2005 as measured by long-term changes in function and health in the U.S. elderly population.

Changes in the health and functioning of the Medicare-enrolled population aged 65+ are tracked by using the 1982-2004/2005 National Long-Term Care Surveys. We found a significant rate of decline in the prevalence of chronic disability that accelerated from 1982 to 2004. These declines are significant for both persons with less severe chronic disability, which might be compensated by modifying the built environment and providing assistive devices, and for persons with more serious disability, which may be affected by reductions in the incidence and severity of disease through biomedical interventions. Declines in chronic disability continued over the 22-year period at a rate fast enough (i.e., 1.52% per annum) to contribute significantly to the long-term fiscal stability of the Medicare (and Medicaid) programs. Changes in the rate and substance of disability declines seem consistent with the intentions of policy interventions in Medicare and Medicaid.

Age Distribution↗
PubMed2005

Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone for an aging population?

Much of the increased risk for atherosclerosis progression with age may be a result of age-related declines in the capacity of precursor cells to repair damage in the arterial endothelium. To estimate the impact of progenitor cell therapy for atherosclerosis on cardiovascular disease (CVD) mortality, life expectancy, and survival, as compared with the lifetime control of conventional risk factors, we modeled the health effects of bone marrow-derived endothelial progenitor cell therapy using data from the 1950 to 1996 follow-up of the Framingham Heart Study. To model cardiovascular disease mortality, we assumed that progenitor cell therapy was applied at age 30, with the effect assumed to be a 10-year delay in atherosclerosis progression. Age projections were constructed analytically using the stochastic process model for risk factor dynamics and mortality and microsimulation techniques. We considered three types of interventions: (i) keeping risk factors within selected limits to model current clinical recommendations; (ii) an age shift of 10 years to model the effects of progenitor cell therapy; and (iii) elimination of a competing risk (such as cancer). Our study suggests that progenitor cell therapy might increase life expectancy in the population as much as the complete elimination of cancer (in females, an additional 3.67 versus 3.37 years; in males, an additional 5.94 versus 2.86 years, respectively).

Adult↗
PubMed2005

Newborn screening for severe combined immunodeficiency (SCID): a review.

Because prompt intervention may prevent complications, early diagnosis is important in many inherited metabolic diseases. Early diagnosis of Severe Combined Immunodeficiency (SCID) is critical - because chances for successful treatment are highest for infants who have not yet experienced severe opportunistic infections. SCID is a rare disease that can be detected in newborn infants (i.e., those more or equal 1 month of age) by automated blood count and manual differential. Early diagnosis of SCID is rare since, because estimates of the incidence rate range from one in 50,000 to 100,000 births, most pediatricians do not routinely count white blood cells in newborns. Tests for T-cell lymphopenia (TCLP) using dried blood spots (DBS) could be used to identify children with SCID - as well as for other immunodeficiencies that would not be apparent until after the child developed an infection. Screening newborns for SCID would allow early diagnosis and treatment -- as well as genetic counseling for the family.

Feasibility Studies↗
PubMed2005

A three-generation approach in biodemography is based on the developmental profiles and the epigenetics of female gametes.

We suggest that there are three premises underlying the need for biodemographic analyses of three-generations: 1.) To describe the structure of the genome, we need to use (apart from mutations) other kinds of heritable changes such as those mediated by facultative elements (variations) and epigenetic alterations. 2.) There are many reasons to analyze individual development and its deviations, such as the biodemographic perspective of fertilization - but also including all long-term intra-generational events of oogenesis and meiosis (beginning with the embryogenesis of the individual's mother - or during the grandmother's pregnancy). 3.) We need to explore the reality that every fertilized egg links - physically and genetically - three successive generations. We focus on genetic and epigenetic events, which start during egg cell lineage determination in F(n-2) gestation and which influence the developmental profile of F(n) generation cohorts. The three-generation approach in epidemiology and biodemography is important so that we might increase our understanding of the effects of environmental forces, such as viral epidemics, and of catastrophes, such as the Chernobyl accident. It is also important for evaluating the processes of senescence and the determinants of human disease.

Animals↗
PubMed2005

The immune system in aging: roles of cytokines, T cells and NK cells.

Aging is characterized by a proinflammatory state that contributes to the onset of disability and age-related diseases. Proinflammatory cytokines play a central role in mediating cellular and physiological responses. The levels of these cytokines may reflect immune system effectiveness. Studies of the effects of aging on inflammatory response show interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to be important. In this review, age-related changes in inflammatory cytokines, T and NK cells, and the biology of IL-6 and TNF-alpha and their relevance to senescence are considered.

Aging↗
PubMed2005

Genome organization and three kinds of heritable changes: general description and stochastic factors (a review).

Due to the increased knowledge of genome architecture, topology, and the mechanisms of hereditary variability, the list of genetic components has grown. This review outlines the general features and principles of genome organization in diverse organisms. The genome codes, stores, and transfers information in both structurally and dynamically. The genome includes two subsystems of genetic elements: obligatory (genes and gene families) and various types of facultative elements which are predominant the content of the human genome. The features of three kinds of heritable changes: mutations, variations (changes in the number or topography of facultative elements), and epigenetic alterations are described. Facultative elements are the first to react to environmental challenges. Together with epigenetic changes, they implement the operational genomic memory. This review discusses both the role of stochastic factors and the transient features of DNA components.

Animals↗
PubMed2005

Whether ionizing radiation is a risk factor for schizophrenia spectrum disorders?

The neural diathesis-stressor hypothesis of schizophrenia, where neurobiological genetic predisposition to schizophrenia can be provoked by environmental stressors is considered as a model of the effects of exposure to ionizing radiation. Analysis of information from electronic databases (MEDLINE, PsycINFO, EMBASE, Current Contents, Elsevier BIOBASE) and hand-made search was carried out. There are comparable reports on increases in schizophrenia spectrum disorders following exposure to ionizing radiation as a result of atomic bombing, nuclear weapons testing, the Chernobyl accident, environmental contamination by radioactive waste, radiotherapy, and also in areas with high natural radioactive background. The results of experimental radioneurobiological studies support the hypothesis of schizophrenia as a neurodegenerative disease. Exposure to ionizing radiation causes brain damage with limbic (cortical-limbic) system dysfunction and impairment of informative processes at the molecular level that can trigger schizophrenia in predisposed individuals or cause schizophrenia-like disorders. It is supposed that ionizing radiation can be proposed as a risk factor for schizophrenia spectrum disorders. The hypothesis that ionizing radiation is a risk factor for schizophrenia spectrum disorders can be tested using data from the Chernobyl accident aftermath. Implementation of a study on schizophrenia spectrum disorders in Chernobyl accident victims is of significance for both clinical medicine and neuroscience.

Brain↗
PubMed2004

Effect of exposure to light-at-night on life span and spontaneous carcinogenesis in female CBA mice.

The effect of constant illumination on the development of spontaneous tumors in female CBA mice was investigated. Fifty female CBA mice starting from the age of 2 months were kept under standard light/dark regimen (12 hr light:12 hr dark; LD) and 50 CBA mice of similar age were kept under constant illumination (24 hr a day, 2,500 Lux, LL). Exposure to the LL regimen decreased food consumption but did not influence body weight, significantly accelerated age-related disturbances in estrous function, and was followed by a significant increase in spontaneous tumor incidence in female CBA mice. Tumor incidence as well as the number of total or malignant tumors was significantly increased in the LL group compared to the LD group (p < 0.001). The incidence of lung adenocarcinomas, leukemias and hepatocarcinomas was 7/50; 6/50 and 4/50 in the LL group and 1/50; 0/50 and 0/50 in the LD group. Mice from the LL groups had shorter life spans then those from the LD group. The data demonstrate, for the first time, that exposure to constant illumination was followed by increases in the incidence of spontaneous lung carcinoma, leukemias and hepatocarcinoma in female CBA mice.

Adenocarcinoma↗
PubMed2004

The role of oxidative damage in mitochondria during aging: a review.

Aging is a complex process (or series of processes). Recent evidence suggests that several of its most important mechanisms are linked by means of cellular damage caused by reactive oxygen species (ROS). Oxidative damage may be a major factor in the loss of physiological functions that occur in degenerative diseases and aging. This is because, in aerobic organisms, the mitochondrial electron transport chain plays an important role in energy production and is a significant source of ROS that damage DNA, RNA, and proteins in cells. While oxidative events in other cell organelles are likely to contribute to the pathobiology of aging, this review highlights alterations in mitochondrial function that, due to accumulated oxidative damage, occur with age.

Aging↗
PubMed2004

Disability trends in gender and race groups of early retirement ages in the USA.

OBJECTIVES: To analyse disability trends over the 1980s-1990s in gender and race groups of early retirement ages in USA. METHODS: Disability trends for white and black males and females aged 65-69 and 70+ are analysed using the 1982-1999 NLTCS. Disability is analysed at three levels (instrumental activities of daily living (IADL), activities of daily living (ADL), and institutionalisation). RESULTS: 1) A larger increase in proportions of non-disabled blacks aged 65-69 compared with whites and males compared with females. 2) Differences in disability trends among gender and race groups. 3) A faster absolute decline in non-institutionalised disabled aged 65-69. 4) A larger absolute decline and a smaller relative decline in proportions of disabled aged 70+ compared with 65-69. 5) A significant decrease in the proportion of ADL disabled blacks and an increase of ADL disabled white females in the age group 70+. CONCLUSIONS: Americans aged 65-69 years manifest a significant improvement in health over the 1980s-1990s but the dynamics differs in gender and race groups. Possible reasons for these differences are discussed.

Activities of Daily Living↗
PubMed2004

Fuzzy set analyses of genetic determinants of health and disability status.

Analyses of complex genotype-phenotype relations require new statistical procedures because of the potentially high dimensionability of those relations which are expressed with both measurement error and stochasticity in the correlation function. We propose modifying a multivariate procedure called grade of membership (GoM) analysis to deal with the special problems of such analyses. In doing so, we make clear some special features of the GoM model for multivariate analysis of high dimensional, discrete data. This is illustrated for apolipoprotein E (APOE) assessments made on 1805 people in the 1999 National Long Term Care Survey. A number of interesting relations with APOE polymorphism were found where disability profiles were more predictive than specific diagnoses because they implicitly contained information on chronicity and severity of disease processes.

Aged↗
PubMed2004

ROS effects on neurodegeneration in Alzheimer's disease and related disorders: on environmental stresses of ionizing radiation.

Neurodegenerative processes associated with Alzheimer's disease are complex and involve many CNS tissue types, structures and biochemical processes. Factors believed involved in these processes are generation of Reactive Oxygen Species (ROS), associated inflammatory responses, and the bio-molecular and genetic damage they produce. Since oxidative processes are essential to energy production, and to other biological functions, such as cell signaling, the process is not one of risk exposure, as for cigarettes and cancer, but one where normal physiological processes operate out of normal ranges and without adequate control. Thus, it is necessary to study the ambiphilicity that allows the same molecule (e.g., beta amyloid) to behave in contradictory ways depending upon the physiological microenvironment. To determine ways to study this in human populations we review evidence on the effects of an exogenous generator of ROS, ionizing radiation, in major population events with radionuclides (e.g., Hiroshima and Nagasaki; Chernobyl Reactor accident; environmental contamination in Chelyabinsk (South Urals) where plutonium was produced, and in the nuclear weapons test area in Semipalatinsk, Kazakhstan). The age evolution, and traits, of neurodegenerative processes in human populations in these areas, may help us understand how IR affects the CNS. After reviewing human population evidence, we propose a model of neurodegeneration based upon the complexity of CNS functions.

Alzheimer Disease↗
PubMed2003

The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice.

The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age-related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER-2/neu transgenic mice. The data demonstrate the regimen-dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER-2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer.

Adenocarcinoma↗
PubMed2003

Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice.

From the age of 3 months until their natural death, female Swiss-derived SHR mice were given melatonin with their drinking water (2 or 20mg/l) for 5 consecutive days every month. Intact mice served as controls. There were 54 mice in each group. The results of this study show that the treatment of melatonin did not significantly influence food consumption, but its administration at lower doses did decrease the body weight of mice; it slowed down the age-related switching-off of estrous function; it did not influence the frequency of chromosome aberrations in bone marrow cells; it did not influence mean life span; and it increased life span of the last 10% of the survivors in comparison to controls. We also found that treatment with low dose melatonin (2mg/l) significantly decreased spontaneous tumor incidence (by 1,9-fold), mainly mammary carcinomas, in mice whereas higher doses (20mg/l) failed to influence tumor incidence as compared to controls. For this reason, we conclude that the effect of melatonin as a geroprotector is dose-dependent.

Animals↗