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After an introduction on the development of biological ageing research in the Netherlands during the past decades, 606 papers on aging published by Dutch institutes in the period 1991-2000, collected from PubMed, were analysed for their relevance to research into biological ageing. For the period 1996-2000, the total number of research papers on biological ageing amounted to 142, which accounts for 23% of all publications on ageing in that period. The number of publications per year did not change. On the basis of these papers and additional information provided by research groups a comprehensive overview of biological ageing research in the Netherlands is presented, together with an extensive literature list. Ageing of the central nervous system (CNS), of the endocrinological system and of the cardiovascular system are the topics most studied. It is concluded that general biological ageing research has not increased in the Netherlands over the last ten years, and that the infrastructure for basic biological ageing research in the Netherlands is weak.

Due to its complexity and its ubiquitous nature the ageing process remains an enduring biological puzzle. Many molecular mechanisms and biochemical process have become synonymous with ageing. However, recent findings have pinpointed epigenetics as having a key role in ageing and healthspan. In particular age related changes to DNA methylation offer the possibility of monitoring the trajectory of biological ageing and could even be used to predict the onset of diseases such as cancer, Alzheimer's disease and cardiovascular disease. At the molecular level emerging evidence strongly suggests the regulatory processes which govern DNA methylation are subject to intracellular stochasticity. It is challenging to fully understand the impact of stochasticity on DNA methylation levels at the molecular level experimentally. An ideal solution is to use mathematical models to capture the essence of the stochasticity and its outcomes. In this paper we present a novel stochastic model which accounts for specific methylation levels within a gene promoter. Uncertainty of the eventual site-specific methylation levels for different values of methylation age, depending on the initial methylation levels were analysed. Our model predicts the observed bistable levels in CpG islands. In addition, simulations with various levels of noise indicate that uncertainty predominantly spreads through the hypermethylated region of stability, especially for large values of input noise. A key outcome of the model is that CpG islands with high to intermediate methylation levels tend to be more susceptible to dramatic DNA methylation changes due to increasing methylation age.

Background-\ud \ud The limited available literature suggests that sleep problems are linked to an increased risk of mild cognitive impairment (MCI). However, this association has been little studied to date in low-income settings.\ud \ud Objective-\ud \ud To investigate the association between sleep problems and MCI in a large sample of adults from six low-and middle-income countries (LMICs).\ud \ud Design-\ud \ud Cross-sectional.\ud \ud Setting-\ud \ud Study on Global Ageing and Adult Health (SAGE).\ud \ud Subjects-\ud \ud 32,715 individuals aged ≥50 years with preservation in functional abilities [age range 50–114 years; 51.7% females].\ud \ud Methods-\ud \ud MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Sleep problems were assessed by the question “Overall in the last 30 days, how much of a problem did you have with sleeping, such as falling asleep, waking up frequently during the night or waking up too early in the morning?” and categorized as “None”, “Mild”, “Moderate”, “Severe/Extreme”. Multivariable logistic regression analysis and meta-analysis were conducted.\ud \ud Results-\ud \ud Compared to no sleep problems, mild, moderate, and severe/extreme sleep problems were associated with significant 1.40, 1.83, and 2.69 times higher odds for MCI with similar associations being observed between age groups and sex. Severe/extreme sleep problems were positively associated with MCI (i.e., OR > 1) in the six countries studied with the overall estimate being OR = 1.80 (95% CI = 1.50–2.16), and a low level of between-country heterogeneity was observed (I2 = 28.2%).\ud \ud Conclusions-\ud \ud Sleep problems were associated with higher odds for MCI. Interventions to improve sleep quality among middle-aged and older adults in LMICs may be an effective strategy in reducing risk of MCI and dementia.

Chronic inflammatory conditions resulting from elevated levels of circulating proinflammatory mediators are common in the elderly. The aim of the paper was to analyze the balance between proinflammatory and anti-inflammatory markers in longevous individuals. The study was conducted in persons aged >90 years old, residents of Poland living either at home or staying at residential care facilities. The study included 90 persons (69 women and 21 men) aged between 90 and 103 years. Persons with abnormal CRP presented with a statistical tendency toward higher fibrinogen and lower IL10 and IL-1α levels compared to patients in whom CRP level was within the normal range. IL-6 concentration predicted abnormality within CRP. Inflammation in persons above the age of 90 years old might be linked to abnormal fibrinogen and IL-6 levels.

Aerobic exercise is associated with changes in brain morphology and improvement of cognitive functions. Physical activity may be especially important after age 60 when cognitive decline is more pronounced. In this paper, the effect of chronic practice of aerobic sports was studied in old adults by assessing their executive and mnesic functions, supported by frontal and temporal brain structures. Two groups were formed according to their age (60–69 and 70–79 years-old) including sportsmen (n = 23) and sedentary men (n = 24). Spatial memory and efficiency of attentional networks were measured, as well as general intelligence. Results showed that sportsmen outperformed sedentary participants in many of the tests employed. Thus their alerting, orienting and executive networks worked more effectively in the ANT-I task for executive functions, and they were more accurate in the spatial memory task, displaying a better spatial orientation. Scores in other neuropsychological tasks followed the same tendency. These data support the protective effect of aerobic exercise on cognitive functions.

Studies of centenarians as a model of successful ageing may help identify various environmental, social, psychological, and genetic factors supporting longevity. The scientific aims of the programme were to assess health status and environmental determinants of ageing of Polish centenarians, and to collect biological material for studying selected aspects of longevity, including genetic factors. The social aim of the project was to bring public attention to ageing of the population, as well as living conditions of elderly individuals. The intention of the authors of this paper is to present aims, scope, methods and preliminary results of the Polish Centenarians Programme, as well as to provide potential new partners for studying various aspects of longevity and ageing with the information about available materials collected during the programme. In this study, 346 subjects aged 100+ were visited, biological material was collected from 285 subjects, and 153 lymphocyte cell lines were immortalized.

Throughout the maturation of germ cells, a morphological, biochemical and functional differentiation of mitochondria has been shown to occur. Ageing is known to cause changes involved in energy metabolism. These changes have been related to molecular and functional alterations in the properties of biological membranes. Variations in membrane lipid composition and lipid-protein interactions occur with ageing in several tissues. The present paper describes the relationship between these membrane alterations and the activities of lipid-dependent enzymes of isolated testis mitochondria in rats of from 10 days of age to 24 months. The specific activities of these enzymes are lower in preparations from adult and aged rats as compared to those from young rats. Temperature breaks of Arrhenius plots show age-dependent shifts to higher temperatures for the NADH-dehydrogenase, succinate-dehydrogenase, cytochrome c oxidase, and ATPase in senescent animals. Analysis of the membrane fatty acid composition reveals a distinct age-dependent fall in the content of polyunsaturated fatty acids accompanied by an increase in the proportion of saturated fatty acids and a decrease in polyunsaturated fatty acid percentage. The results suggest that during spermatogenesis and the ageing process some changes in the composition of the fatty acids in the surrounding membrane affect the protein-lipid interactions, producing a decrease in mitochondrial enzyme activities.

An analysis of the current situation in Russian biogerontology is presented in this paper. There are several active groups in Russia pursuing research in biogerontology capable of producing results publishable in international journals of high repute. The main directions of research on the biology of ageing in this country are prevention of premature ageing, the role of free radicals and of the endocrine system (in particular, the pineal gland) in the mechanisms of ageing, carcinogenesis and ageing and population genetics of ageing. Several groups are conducting fruitful research on the theoretical aspects of the biology of ageing. Only a few teams are focusing on molecular biology and the genetics of ageing. In the past few years, many more researchers in fields highly relevant to gerontology have been attracted by issues in gerontological research. In Russia, the most basic problem facing researchers in biogerontology and other relevant areas is an almost complete absence of support from the State and other decision makers.

The paper discusses some data and arguments in support of the hypothesis that age- associated elevation of the threshold of sensitivity of the hypothalamo-pituitary complex to homeostatic stimuli, plays a major part in the mechanism of development, ageing and age-pathology formation. The decline in the hypothalamic levels of biogenic amines, i.e. one of the factors producing changes in the hypothalamic “set point” of sensitivity in the reproductive, energy and adaptive homeostats, is likely to be directly responsible for the increased incidence of mental depression, essential hypertension and disturbances in appetite regulation with advancing age. The disturbed rhythms of functioning of the three main homeostats results in a shift toward a predominant utilization of free fatty acids (FFA) rather than glucose for energy supply. This shift plays an important role in the mechanism of ageing, age-associated obesity, adult-onset diabetes mellitus, metabolic immunodepression and cancrophilia. Eventually, elevation of the hypothalamic threshold of sensitivity in higher organisms, man included, makes a considerable contribution to the transformation of the developmental program into the mechanism of natural death, which may be defined as regulatory type of death. Arguments are adduced to show that external environmental factors, e.g. overfeeding, stressors, excessive lighting, exposure to some chemical carcinogens, etc. contribute to the development of this hypothalamic phenomenon and/or to the pre-dominant utilization of FFA for energy supply, and therefore they are responsible for the intensification of body development, ageing and formation of specific age pathology. Some contreversial aspects of the hypothesis and traditional concepts of present-day gerontology are discussed. At present it is possible to male more general conclusions based on the data discussed in this article. If the stability of internal environment of the organism provides the body with a certain degree of functional freedom from the variability of external and internal environmental factors, the programmed deviation of homeostasis is an essential condition of development of organism. Therefore, alongside the Law of Constancy of Internal Environment, there exists the Law of Deviation of Homeotasis. In a new context, hypothalamic alterations occuring in the course of ontogenesis provide a mechanism by which the implementation of the Law of Deviation of Homeostasis is ensured. Therefore, it does not really matter that the hypothalamic threshold of sensitivity to regulation signals may be elevated (Parts I, II and III) or, in some systems, may be lowered (Parts III and IV). What actually matters is that in both cases a programmed deviation of homeostasis takes place (Dilman, 1979).

A consideration of the distribution of nuclei of high euploidy levels in diploid organisms such as mammals indicate that they characterise cells which are relatively long-lived. It is the purpose of this paper to examine the possible relevance of polyploidy as a strategy for reducing the rates at which deleterious events affect long-lived cells, and hence its effect on cell ageing, with special reference to the mammalian liver as a possible model system.

The paper describes changes in the interrenal gland of a laboratory-bred population of Lebistes reticulatus (Peters) throughout life. Changes in the volume of the interrenal tissue, the height of the interrenal cells, and interrenal nuclear volume were measured; and detailed recordings of cytological characteristics were kept. Differences were found between female and male fish. In young female Lebistes the interrenal tissue was disposed in long cords of cuboidal or polygonal cells, with sparse cytoplasmic granulation. With increasing age there was a tendency for the volume of the interrenal gland to increase, whilst there was a steady fall in cell height and also a decline in the volume of the nucleus. There was a marked increase with age in cytoplasmic granulation of the interrenal cells, with nuclear changes apparent in the increased staining reaction and pycnosis of the nuclei. In young male Lebistes the arrangement of the interrenal gland, which occurred more anteriorly than in female fish, was principally in groups of polygonal cells containing pale-staining granules. With advancing age there was a marked increase in the volume of the gland, whilst the volume of the cell nucleus fell. There was no change in interrenal cell height with age, and only a slight increase in cytoplasmic granulation. Interrenal cells with pycnotic nuclei were more numerous in old male fish than in old females. Chromaffin tissue occurred as small groups of pale-staining cells surrounded or bordered by interrenal cells. There was no evidence of any marked change in the amount of chromaffin tissue with age; great individual variations were found throughout life. Chromaffin cells with an unusually large basophilic nucleus were recorded in old fish of both sexes. The general impression was one of decreasing interrenal activity with age; the increased granulation was considered to be associated with degeneration and pycnosis of cells, rather than with increased secretory activity. The appearance of the gland in old age was similar to that found in hypophysectomized fish, and it was suggested that the ageing changes in the interrenal tissue of Lebistes may reflect a gradual decrease in the secretion of adrenocorticotrophic hormone by the ageing pituitary gland.

Reciprocal hybrids of two highly inbred strains of Drosophila melanogaster , Gabarros 4 and Abeele, were cultured, at a preimaginal population density of 30 eggs per standard vial at the temperatures of 16, 19, 22, 25, 28 and 31°C. Afterwards for every preimaginal temperature considered and for the whole life, the daily egg-production of females of known size and duration of development was counted, at 25°C. Life-span was also recorded. The mean total fecundity does not vary in function of the preimaginal temperature, exception made for the extreme 31°C. The mean daily egg-production, the size and the duration of development decrease with the increase in preimaginal temperature. Life-span at 25°C is prolonged when that temperature is decreased; life-span is thus positively correlated with size and duration of development. In a previous experiment, the life-span at 25°C of hybrids cultured at 25°C and at various preimaginal population densities was positively correlated with duration of development and negatively with size. The regressions longevity-duration of development observed in both experiments are of an identical sign; they differ however significantly. It is therefore concluded that longevity is not determined solely by preimaginal duration of development and that more of one developmental factor must be involved. The next paper in the series will compare and discuss the results of both experiments.

Szent-Gyorgi and coworkers reported the existence, in various vegetable and animal tissues, of cellular growth inhibitors, glyoxal derivatives with the general formula R-CO-CHO. They appear to act by way of an interference with protein synthesis, by forming a bound between the inhibitor and -SH groups of cellular compounds essential to normal protein synthesis. In the present paper we investigated the inhibitor concentration in the liver and brain of rats as a function of age and of treatment with Folcysteine, which release in the body active -SH groups. Our results indicated significant differences between the concentration of the inhibitors in the hepatic tissue of rat of different ages. In old animals the concentrations are about 62 percent greater than in young. In brain, the inhibitor concentration differences are much smaller, but still significant. This phenomenon might be involved in protein synthesis modification in old age and in a biochemical mechanism of the ageing process.