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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.

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.

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 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.

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.

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.

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., (Copyright 2002 Wiley-Liss, Inc.)