Biological age and tempos of aging in women over 60 in connection with their morphofunctional characteristics

Background

The study of aging processes and the changes in morphological, physiological, and functional characteristics that are associated with aging is of great interest not only for researchers, but also for the general public. The aim of the present paper is to study the biological age and tempos of aging in women older than 60 years, including long-lived females (over 90-years-old), and their associations with morphofunctional characteristics.

Results

Somatic traits, body mass components, and functional characteristics were investigated in 119 elderly (between 60 and 74-years-old) and long-lived (over 90-years-old) women in Tiraspol. With the special PC software ‘Diagnostics of Aging: BioAge’ (National Gerontological Center, Moscow, Russia) the biological age and tempos of aging were evaluated in the study participants. The results show close connections between morphofunctional changes, particularly in body mass components, and biological age. The software demonstrated its validity in the estimation of biological age in the group of elderly women. In the homogenous (according to their chronological age) group of women, three subgroups were separated with different tempos of aging: those with lower rates of aging (biological age less than chronological age by two years or more); those consistent with their chronological age, and those with accelerated tempos of aging (biological age higher than chronological age by two years or more).

Conclusions

Morphofunctional characteristics in the studied groups of women demonstrate the trends of age-involutive changes which can be traced through all groups, from those with slow rates of aging, to those with average rates, to those with accelerated tempos of aging, and finally in long-lived women. The results of comparative analysis show that women with accelerated aging are characterized with such traits as lower skeletal muscle mass, lower hand grip strength, and higher metabolic rate. Canonical discriminant analysis revealed a number of morphofunctional characteristics which differentiate the early-aging women from women with average rates of aging: higher BMI values, excessive fat mass, lower skeletal muscle mass and low values of hand grip strength. Thus the presence of such characteristics in elderly women can be considered as additional risk factor towards the early onset of the aging process.     

Radiographic incidence of spinal osteopathologies in captive rhesus monkeys (Macaca mulatta)

Degenerative spinal disease is a leading cause of chronic disability both in humans and animals. Although widely seen as a normal occurrence of aging, degenerative spinal disease can be caused by various genetic, iatrogenic, inflammatory, and congenital factors. The objective of this study was to characterize the degenerative spine-related diseases and the age at onset in a random subpopulation of 20 captive rhesus monkeys (Macaca mulatta; male, 13; female, 7; age: range, 4 to 27 y; median, 18.5 y). Spinal radiographic evaluation (left lateral, right lateral, and ventrodorsal views) of the spinal column (C1 to S1) was performed, and spinal degenerative disease was scored. The incidence of osteopathology was higher in the 14- to 18-y-old group, but incidence did not differ according to sex. In the studied population, degenerative changes were present in monkeys as young as 9 y of age.     

海洋生物资源开发研究概况与展望

对各类主要的海洋生物资源开发研究作了简洁概述,从海洋生物体内获取的各种活性物质,除可研究海洋药物外,还可开发海洋生物功能性保健品,海洋生物化工产品等;此外,尚可利用其特异的化学结构作为先导物,设计合成治疗疑难病的创新药物。可以预言,２１世纪将是人类研究、开发、利用海洋生物资源的黄金时代     

Potential biomarkers of ageing

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities.Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.     

Human age reversal: Fact or fiction?

Although chronological age correlates with various age‐related diseases and conditions, it does not adequately reflect an individual''s functional capacity, well‐being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age‐related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant‐based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non‐interventional studies have connected high‐quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha‐ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans. Additional research is warranted to better understand these computational models and the clinical significance of lowering or reversing their outputs.     

The effects of normal aging on myelin and nerve fibers: A review

It was believed that the cause of the cognitive decline exhibited by human and non-human primates during normal aging was a loss of cortical neurons. It is now known that significant numbers of cortical neurons are not lost and other bases for the cognitive decline have been sought. One contributing factor may be changes in nerve fibers. With age some myelin sheaths exhibit degenerative changes, such as the formation of splits containing electron dense cytoplasm, and the formation on myelin balloons. It is suggested that such degenerative changes lead to cognitive decline because they cause changes in conduction velocity, resulting in a disruption of the normal timing in neuronal circuits. Yet as degeneration occurs, other changes, such as the formation of redundant myelin and increasing thickness suggest of sheaths, suggest some myelin formation is continuing during aging. Another indication of this is that oligodendrocytes increase in number withage. In addition to the myelin changes, stereological studies have shown a loss of nerve fibers from the white matter of the cerebral hemispheres of humans, while other studies have shown a loss of nerve fibers from the optic nerves and anterior commissure in monkeys. It is likely that such nerve fiber loss also contributes to cognitive decline, because of the consequent decrease in connections between neurons. Degeneration of myelin itself does not seem to result in microglial cells undertaking phagocytosis. These cells are probably only activated when large numbers of nerve fibers are lost, as can occur in the optic nerve.     

Epigenetic age prediction

Advanced age is the main common risk factor for cancer, cardiovascular disease and neurodegeneration. Yet, more is known about the molecular basis of any of these groups of diseases than the changes that accompany ageing itself. Progress in molecular ageing research was slow because the tools predicting whether someone aged slowly or fast (biological age) were unreliable. To understand ageing as a risk factor for disease and to develop interventions, the molecular ageing field needed a quantitative measure; a clock for biological age. Over the past decade, a number of age predictors utilising DNA methylation have been developed, referred to as epigenetic clocks. While they appear to estimate biological age, it remains unclear whether the methylation changes used to train the clocks are a reflection of other underlying cellular or molecular processes, or whether methylation itself is involved in the ageing process. The precise aspects of ageing that the epigenetic clocks capture remain hidden and seem to vary between predictors. Nonetheless, the use of epigenetic clocks has opened the door towards studying biological ageing quantitatively, and new clocks and applications, such as forensics, appear frequently. In this review, we will discuss the range of epigenetic clocks available, their strengths and weaknesses, and their applicability to various scientific queries.     

Aging, evolution and individual health span: introduction

The effect of autologous and environmental wear and tear on genes and gene products will be considered in systems renewed by self-replicating stem and precursor cells as well as in systems that do not have the capacity for self-renewal. Aging will be discussed in terms of speciation and in terms of health-span differences between individuals of the same species. The analysis of speciation involves early as well as late-acting genes. The intraspecies analysis is primarily concerned with the second half of life and thus is not affected by selective pressures. Analysis of individual aging is concerned with health span, qualified by identification of the particular system that is responsible for the limit of health span in subpopulations; it depends on a subset of allelic products of many genes and their relative functional capacity. The identification of such alleles can provide the starting point for reverse genetics. Results will be presented, which have been obtained by analysis of age-related events in inbred mice, where regulation, involved in degenerative disease of old age, can be studied in groups of individuals with a relatively constant genetic background. It should be possible to identify appropriate probes for degenerative diseases of old age that can be used for detection of corresponding human genes. Worldwide demographic changes have created the need for a new type of public health policy. To respond to this need, we should learn how to identify individuals at risk from degenerative diseases of old age and how to treat them preventively.     

Barriers to mesenchymal stromal cells for low back pain

Intervertebral disc degeneration is the main cause of low back pain. In the past 20 years, the injection of mesenchymal stromal cells (MSCs) into the nucleus pulposus of the degenerative disc has become the main approach for the treatment of low back pain. Despite the progress made in this field, there are still many barriers to overcome. First, intervertebral disc is a highly complex load-bearing composite tissue composed of annulus fibrosus, nucleus pulposus and cartilaginous endplates. Any structural damage will change its overall biomechanical function, thereby causing progressive degeneration of the entire intervertebral disc. Therefore, MSC-based treatment strategies should not only target the degenerated nucleus pulposus but also include degenerated annulus fibrosus or cartilaginous endplates. Second, to date, there has been relatively little research on the basic biology of annulus fibrosus and cartilaginous endplates, although their pathological changes such as annular tears or fissures, Modic changes, or Schmorl's nodes are more commonly associated with low back pain. Given the high complexity of the structure and composition of the annulus fibrosus and cartilaginous endplates, it remains an open question whether any regeneration techniques are available to achieve their restorative regeneration. Finally, due to the harsh microenvironment of the degenerated intervertebral disc, the delivered MSCs die quickly. Taken together, current MSC-based regenerative medicine therapies to regenerate the entire disc complex by targeting the degenerated nucleus pulposus alone are unlikely to be successful.     

Correlation of Matrix Metalloproteinases-1 and Tissue Inhibitor of Metalloproteinases-1 with Patient Age and Grade of Lumbar Disk Herniation

The authors studied the nuclear magnetic resonance films and the expression of MMP-1 and TIMP-1 in disk specimens’ of patients who had undergone operations for lumbar disk herniation. Forty-one lumbar disk patients were evaluated imaging for degenerative changes and their disk specimens immunohistochemical expression of MMP-1 and TIMP-1. The degree of degenerative changes was based on magnetic resonance imaging films. Sections of disk immunostained for MMP-1 and TIMP-1 were evaluated semiquantitatively. Patients were categorized in three age groups: <30 years, from 30 to 60 years, and >60 years of age. The expressions of MMP-1 and TIMP-1 were related to patients’ age and degree of degenerative changes. There were statistical differences in the expression of MMP-1 and TIMP-1 between the age and degree of degenerative changes groups. With the degree of degenerative changes, the expression of MMP-1 and TIMP-1 increased obviously. But in old age group, the expression of MMP-1/TIMP-1 was higher than the young groups. The expressions of MMP-1 and TIMP-1 were strongly correlated to the age and the degree of the degenerative changes. An important finding in this study is the unbalance of the expression of MMP-1 and TIMP-1 along with the growth of the age.     

Is Life Law-Like?

Genes are generally assumed to be primary biological causes of biological phenotypes and their evolution. In just over a century, a research agenda that has built on Mendel's experiments and on Darwin's theory of natural selection as a law of nature has had unprecedented scientific success in isolating and characterizing many aspects of genetic causation. We revel in these successes, and yet the story is not quite so simple. The complex cooperative nature of genetic architecture and its evolution include teasingly tractable components, but much remains elusive. The proliferation of data generated in our "omics" age raises the question of whether we even have (or need) a unified theory or "law" of life, or even clear standards of inference by which to answer the question. If not, this not only has implications for the widely promulgated belief that we will soon be able to predict phenotypes like disease risk from genes, but also speaks to the limitations in the underlying science itself. Much of life seems to be characterized by ad hoc, ephemeral, contextual probabilism without proper underlying distributions. To the extent that this is true, causal effects are not asymptotically predictable, and new ways of understanding life may be required.     

Tissue engineering strategies applied in the regeneration of the human intervertebral disk

Low back pain (LBP) is one of the most common painful conditions that lead to work absenteeism, medical visits, and hospitalization. The majority of cases showing signs of LBP are due to age-related degenerative changes in the intervertebral disk (IVD), which are, in fact, associated with multiple spine pathologies. Traditional and more conservative procedures/clinical approaches only treat the symptoms of disease and not the underlying pathology, thus limiting their long-term efficiency. In the last few years, research and development of new approaches aiming to substitute the nucleus pulposus and annulus fibrosus tissue and stimulate its regeneration has been conducted. Regeneration of the damaged IVD using tissue engineering strategies appears particularly promising in pre-clinical studies. Meanwhile, surgical techniques must be adapted to this new approach in order to be as minimally invasive as possible, reducing recovering time and side effects associated to traditional surgeries. In this review, the current knowledge on IVD, its associated pathologies and current surgical procedures are summarized. Furthermore, it also provides a succinct and up-to-date overview on regenerative medicine research, especially on the newest tissue engineering strategies for IVD regeneration.     

Disulfide bond formation and its impact on the biological activity and stability of recombinant therapeutic proteins produced by Escherichia coli expression system

Therapeutic proteins require correct disulfide bond formation for biological activity and stability. This makes their manufacturing and storage inherently challenging since disulfide bonds can be aberrantly formed and/or undergo significant structural changes. In this paper the mechanisms of disulfide bond formation and scrambling are reviewed, with a focus on their impact on the biological activity and storage stability of recombinant proteins. After assessing the research progress in detecting disulfide bond scrambling, strategies for preventing this phenomenon are proposed.     

Induction of the cytoplasmic 'petite' mutation by chemical and physical agents in Saccharomyces cerevisiae.

A range of physical and chemical agents induce the mitochondrial 'petite' mutation in the yeast Saccharomyces cerevisiae. DNA intercalating agents as well as chemicals which can interfere with DNA synthesis induce this mutation, but only in growing cells. Many chemical or physical agents that produce a DNA lesion which is not simply reversed can induce various levels of the petite mutation, and may be more effective in non-growing cells. A limited number of chemicals act like ethidium bromide, inducing a high frequency of petites which is partially reversible with increasing concentration or time. The ability of a specific compound to be transported into mitochondria or its affinity for AT base pairs in DNA may determine whether it acts primarily as a nuclear or mitochondrial mutagen. In mammalian cells, some neoplastic changes occur at the mitochondrial level. Analogies between yeast and mammalian mitochondria suggest that agents which increase petite mutagenesis in yeast may have some carcinogenic potential. Although some types of petite inducer may have potential as antitumour drugs, those which are very effective antimitochondrial agents appear to be too toxic for therapeutic use. A process comparable to early stages in petite mutagensis occurs in human degenerative diseases and it seems possible that a consequence of exposure to petite mutagens could be an increase in the rate of degenerative diseases or of the aging process.     

中枢疲劳研究与思考

中枢疲劳既可以作为独立疾病影响人们的日常工作和学习,又可以作为症状出现于多种慢性疾病,其定义和机制国内外说法不尽相同。中枢疲劳是由于中枢神经系统发生退行性或其他不良变化,从而导致躯体、神经、包括心理一系列的疲劳样反应。其机制涉及到中枢神经系统和外周传导系统等多个维度、多个节点的变化,充分把握中枢疲劳的概念本质及潜在生物学机制对其临床防治有着重要理论和实践意义。此外,动物模型作为基础研究的前提和必要工具是中枢疲劳研究过程中又一重要问题。本文在文献整理的基础上,先从定义的角度出发由疲劳引申到中枢疲劳,将现阶段对中枢疲劳的不同概念阐述做一分析,并从机制和动物模型两个方面展开对国外研究进展进行综述。     

The evolution of human biosocial behaviour

The analysis of human behaviour can be approached from three different but complementary perspectives: the first includes the eternal debate about the degree of environmental or genetic determinism of social behaviour; the second, in the context of evolutionary ecology, concerns the evaluation of behavioural responses to morphological and/or environmental changes that have been the key to success in our species; the third, in the context of the analysis of the biology of the health of modern day populations, deals with the biological consequences of social behavioural changes. The secret of the success of a species resides in its capacity to respond behaviourally to the morphological and environmental changes produced during its biological history. What is unique about humans concerns our brains and their derived function: flexible behaviour. The morphological, physiological and behavioural changes that allow thecreation and maintenance of such a large brain are intimately connected to reproduction and therefore to the biosociology of women, the members of the speciesHomo sapiens in whom are combined, with notable success, a prolonged life-cycle, some anatomical and physiological traits and flexible reproductive behaviour, which together confer a decisive demographic advantage on them over other hominids. In summary, as well as contributing to the spread of this information by which women can make informed decisions based on a knowledge of causes, with the aim of optimizing our health it is necessary to consider the possibility of approaching some aspects of our biology and behaviour as patterns fixed by evolution. Three factors would be the most easily adjustable for this purpose: a) to delay the age of sexual maturation, b) to bring forward the age of first maternity, and c) to encourage breastfeeding on demand without substitutes and for a 3–5 month period.     

Fat-soluble vitamin and phytochemical metabolites: Production,gastrointestinal absorption,and health effects

Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.     

Efficient two-sample designs for microarray experiments with biological replications

In the last years, biostatistical research has begun to apply linear models and design theory to develop efficient experimental designs and analysis tools for gene expression microarray data. With two-colour microarrays, direct comparisons of RNA-targets are possible and lead to incomplete block designs. In this setting, efficient designs for simple and factorial microarray experiments have mainly been proposed for technical replicates. But for biological replicates, which are crucial to obtain inference that can be generalised to a biological population, this question has only been discussed recently and is not fully solved yet. In this paper, we propose efficient designs for independent two-sample experiments using two-colour microarrays enabling biologists to measure their biological random samples in an efficient manner to draw generalisable conclusions. We give advice for experimental situations with differing group sizes and show the impact of different designs on the variance and degrees of freedom of the test statistics. The designs proposed in this paper can be evaluated using SAS PROC MIXED or S+/R lme.