The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.     

Glucose-mediated cross-linking of collagen in rat tendon and skin

BACKGROUND: Cross-linking of macromolecules like collagen plays an important role in the development of complications in diabetes and ageing. One of the underlying mechanisms of this cross-linking is the formation of advanced glycation endproducts (AGEs). METHODS: In this study, we assessed the use of differential scanning calorimetry (DSC) for the determination of these cross-links and the effects of an AGE inhibitor and breaker. RESULTS: Treatment with N-phenacylthiazolium bromide (ALT-711) of diabetic rats with 2 months duration of diabetes normalized large artery stiffness, assessed by characteristic input impedance and systemic arterial compliance, but with the use of DSC, no statistical difference in cross-linking between control and treated animals could be measured. In addition, we performed in vitro incubation of collagen preparations with ribose and glucose to assess the DSC method as well as the influence of AGE breakers and inhibitors. Incubation of rat tail tendon (RTT) with 100 mmol/l glucose showed an increase in collagen cross-linking expressed as an increase in shrinkage temperature (T(s)). Addition of aminoguanidine (AG), an inhibitor of AGE formation, prior to glucose incubation showed a slower increase of the amount of glucose-derived cross-linking. Replacing glucose with ribose showed a quicker increase in cross-linking and less effect on cross-linking by adding aminoguanidine, demonstrating the higher reactivity of pentoses above hexoses. Similar experiments with rat skin samples (RSS) showed that RSS (type III collagen) are less susceptible to glucose-mediated cross-linking than RTT (type I collagen). We observed no effect of addition of ALT-711, a breaker of glucose-derived cross-links, on the extent of collagen cross-linking in both RTT and RSS. CONCLUSION: Overall, DSC is considered a useful method for assessing glucose-mediated cross-linking in vitro with nonphysiological glucose concentrations. The in vivo use in biological samples is limited due to the lack of sensitivity. However, DSC remains a quick and well-quantitated method in comparison with other methods, like enzymatic digestibility.     

The amino- and carboxyterminal cross-linked telopeptides of collagen type I, NTX-I and CTX-I: a comparative review

Bone diseases such as osteoporosis or bone metastases are a continuously growing problem in the ageing populations across the world. In recent years, great efforts have been made to develop specific and sensitive biochemical markers of bone turnover that could help in the assessment and monitoring of bone turnover. The amino- and carboxyterminal cross-linked telopeptides of type I collagen (NTX-I and CTX-I, respectively) are two widely used bone resorption markers that attracted great attention due to their relatively high sensitivity and specificity for the degradation of type I collagen, and their rapid adaptation to automated analyzers. However, the clinical performance of both markers differs significantly depending on the clinical situation. These differences have caused considerable confusion and uncertainty. If used correctly, both markers have great potential to improve the management of many bone diseases. We here review the biochemistry, analytical background and clinical performance of NTX-I and CTX-I, as documented in the accessible literature until March 2008.     

A novel engineered dermis for in vitro photodamage research

The realization of biologically relevant human tissue equivalents as an in vitro model to investigate human diseases, as well as to test the efficacy or toxicity of novel compounds, is emerging as a new challenge in tissue engineering. Currently, the in vitro three‐dimensional (3D) dermis model mainly involves the use of cells embedded in exogenous non‐human matrices. However, such models feature biological and functional disparities with native dermis, therefore limiting their relevance to the in vivo situation. The purpose of this study was to provide a reliable endogenous human dermal equivalent (HDE) able to recapitulate the extracellular matrix (ECM) remodelling of the native dermis occurring after external damage. To this end, UVA irradiation was used to induce photodamage to both the HDE and to a fibroblast‐populated collagen matrix. The photodamage was investigated at the cellular and ECM level and the results showed that, although a cellular response was detected in both systems, no ECM reorganization characteristic of the in vivo photo‐aged dermis could be detected in the fibroblast‐populated collagen matrix. In contrast in the HDE, the neosynthesized ECM recapitulated the characteristic ageing behaviour of the dermis found in vivo, in terms of collagen and hyaluronic acid synthesis as well as collagen organization remodelling. This study therefore demonstrates the role of the endogenous ECM in recapitulating in vitro the functionality of the human dermis and the proposed HDE as a novel tool for photoprotection trials. Copyright © 2016 John Wiley & Sons, Ltd.     

Reexamining the boundaries of the 'normal' in ageing

Textbooks and policy documents tend to present the boundary between normal and abnormal ageing as natural and clearly demarcated. In this study, we trouble the notion of natural and clearly demarcated boundaries between normal and abnormal ageing by considering how these boundaries have been established and maintained in present-day Western contexts. We draw on both Canguilhem's discussion of the normal and the abnormal and Foucault's emphasis on the role of the sociohistorical context in the social practice of boundary generation. In doing so, we critically examine common conceptualizations of normal and abnormal ageing, including those found in antiageing science, successful ageing and healthy ageing policy discourses and in health education textbooks. We argue that the growing emphasis on 'healthy' ageing both reflects and shapes the societal views of those individuals who are not able to remain disease-free and represents a kind of mystification of ageing where ageing without functional or cognitive decline is instituted as the norm. Awareness of the role that the social context plays in shaping definitions of normal and abnormal ageing encourages critical consideration of the effects that Western conceptualizations of normal ageing may have for older adults who continue to age with cognitive or functional decline.     

Change in the static rheological properties of the aorta in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits with progress of atherosclerosis

The rheological properties of the arterial wall have intimate connections with the fine structure of the wall. Alteration in fine structure due to cardiovascular disease, such as atherosclerosis, could affect the rheological characteristics of the wall. The present study was designed to investigate changes in the static rheological properties of the aorta in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits aged 10-12, 22-24 and 34-36 months in relation to histological alteration of the wall due to progression of atherosclerosis with age. Circumferential wall strips were excised from the ascending, proximal descending thoracic and proximal abdominal aortas and their stress/strain relationship was recorded. Tensile force of the wall showed a slight but insignificant decrease in the KHC rabbit group aged 10-12 months compared to that in the age-matched control group in the proximal thoracic aorta and increased significantly with ageing in the KHC rabbits in these aortic regions mainly at medium and high strain ranges. Wall stress was significantly smaller in the 10-12 months old KHC rabbit group than in the age-matched control group in the proximal thoracic and proximal abdominal aortas and increased significantly with ageing in the KHC rabbit groups chiefly at medium and high strain ranges. Incremental elastic modulus determined at 50% stretching of the initial length of the wall strip was also significantly lower in the KHC rabbit group aged 10-12 months in comparison to that in the age-matched control group and increased significantly with ageing in the KHC rabbit group. The intima thickened severely with abundant foam cells in the KHC rabbits aged 10-12 months. With increasing age, collagen and elastin fibres showed signs of gradual proliferation among the foam cells. The aortic wall in KHC rabbits was viscoelastic in the relatively early stage of atherosclerosis due to abundant foam cells, and thereafter increased in stiffness gradually with fibrous proliferation and calcification. We can conclude that the static rheological properties of the atherosclerotic aortic wall changed in association with alteration in the microstructure of the wall with progression of atherosclerosis.     

The process of ageing

An increasing elderly population involves nurses with older people in a wide sphere of activities. It is essential that an understanding of ageing and its effects is included as part of the knowledge which is common to all nurses. The study of gerontology has intensified in recent years but an interest in the phenomenon of ageing can be traced back through the centuries. A number of theories about the causes of ageing have been put forward but the evidence in support of these is still inconclusive. Control of the ageing process remains beyond mankind, but it is known that environmental and hereditary factors contribute to the rate of ageing.
Knowledge about the effects of ageing is accumulating. The influence of ageing on the functions of the body can be measured. Most functions are reduced in efficiency and the lowered levels of performance have to be considered in their relation to the medical and nursing care of older people.
Ageing also has psychological and social implications. Changes in behaviour patterns can occur as a result of the influence of ageing on personality, intellect and memory. There are also changes in the social circumstances of older people resulting from such factors as retirement and bereavement.
The growing problem of an elderly population is stimulating increasing research into the causes and effects of ageing.     

Testosterone supplementation,glucocorticoid milieu and bone homeostasis in the ageing male

Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone‐induced changes in the glucocorticoid output could serve as a determinant of bone‐related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone‐induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic–pituitary–adrenal axis feedback loop operativeness during testosterone supplementation, represents a well‐balanced bone‐related therapeutic update.     

Preeclampsia-associated alterations in sphingolipid composition of the umbilical cord artery

ObjectivesPreeclampsia, the most common pregnancy-associated pathological syndrome, is accompanied by significant remodelling of the extracellular matrix and alteration in lipid composition of the umbilical cord artery (UCA).Design and methodsWe evaluate the sphingolipid composition of UCA and its alteration in preeclampsia. Thin layer chromatography, solid-phase extraction and high-performance liquid chromatography were employed for these analyses.ResultsThe UCA wall is abundant in sphingomyelins and ceramides, whereas the amounts of sphingoid bases are rather low. Preeclampsia is associated with significant increases in sphingomyelins and sphinganine with a decrease in ceramides and other sphingoid bases.ConclusionsSphingoids, as secondary messengers, may evoke preeclampsia-associated decrease in hyaluronate and accumulation of collagen, sulphated glycosaminoglycans and cholesterol in the UCA wall. This we propose corresponds to an “early ageing” of the umbilical cord and may be a potential mechanism by which preeclampsia evokes an initiation of hypertension in utero and its amplification through childhood and adult life.     

The use of emollient therapy for ageing skin

Skin ageing has intrinsic signs and symptoms, often complicated by extrinsic photo-ageing symptoms and concurrent disease processes. It progresses with age but varies between individuals and its symptoms are numerous. Skin ageing has physical and psychosocial repercussions that can influence coping. Emollient therapy can help to reduce two symptoms--dryness and loss of the skin's barrier function. Better understanding of skin ageing and the usefulness of emollients can be reinforced by education and encouragement from healthcare professionals. Such interventions should encourage self-management and confidence in using emollients. The partnership between healthcare professionals and older people helps to overcome co-existent ageing difficulties, such as cognitive impairment, hearing loss and impairment of manual dexterity and mobility, which enhances self-reliance.     

Research into ageing and older people

AIM: The aim of this paper is to consider the process of ageing, the effects of ageing and research related to ageing. BACKGROUND: In most countries of the world, the UK being no exception, the population is ageing in terms of the absolute numbers of and relative proportion of older people. This has resulted from economic, scientific and medical progress. However, it poses challenges for health and social services. METHOD: Selective review of the literature. CONCLUSION: Ageing is an inevitable part of life and, while not in itself debilitating, can be accompanied by a range of debilitating physical and mental conditions which lead to frailty and dependency. There is limited evidence that the ageing process can be alleviated, as such, but there is some evidence that choices and circumstances in early life can influence the extent to which we age successfully. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers have two responsibilities with regard to age: they are increasingly engaged in organizing care for older people in acute and long-term settings and in nursing homes and the more they need to understand the process of ageing. They also have responsibilities towards their workforce and can facilitate lifestyle choices which may help their workforce to age successfully.     

Seeking a balance between employment and the care of an ageing parent

Scand J Caring Sci; 2011; 25; 285–293
Seeking a balance between employment and the care of an ageing parent Rationale: A growing number of middle‐aged people are engaged in informal care of their parents while employed. To provide support as employers, co‐workers or staff, health care professionals need insight into the experiences of people managing these responsibilities. Aim: To elucidate the experience of providing informal care to an ageing parent while managing the responsibilities of a working life. Methods: Narrative interviews were performed with 11 persons with experience of the phenomenon. Transcribed interviews were analysed with phenomenological hermeneutics. Ethics: Informed consent was given prior to the interviews. The study was approved by a research ethics committee. Findings: Providing informal care to an ageing parent while also pursuing a working life implies seeking balance: a balance between providing support to the parent’s needs and one’s responsibilities at work. Being employed supports this balance as it provides both fulfilment and refuge. Being capable of managing both roles grants a sense of satisfaction, supporting one’s sense of balance in life. The balance can be supported by sharing the responsibility of caring for the ageing parent with others. Study limitations: Despite perceived saturation and an effort to provide for the possibility to consider internal consistency, the findings should be considered as a contribution to the understanding of the phenomenon, as experienced by individuals in their life world. Conclusions: It is essential to recognise the impact that providing care for an ageing parent may have on the lives of a growing number of people, particularly if they have employment responsibilities. Acknowledgement by others supports one’s ability to attain balance; as co‐workers and managers, we can acknowledge the efforts of an informal caregiver and as health care staff recognise the valuable contribution made by people in mid‐life who provide informal care for their ageing parents.     

Culture and ageing: reflections on the arts and nursing

AIM; In this paper, we focus on ageing as an area in which nursing, society and the humanities can be profitably conjoined. We illustrate our argument with three case studies of ageing: in painting, opera and ballet. BACKGROUND: There has been a recent spectacular increase in papers devoted to the relatively new field of the medical humanities. We argue for a similar renaissance in thinking about the connections between the arts and nursing. DISCUSSION: First, we consider the paintings of J.M.W. Turner (1775-1851) as examples of loss, ageing and death. Second, we draw upon Leos Janácek's opera 'The Makropulos Case' (1926) as a focus for debate about human mortality. Third, we review some ethnographic research on the balletic body as an example of cultures of youthful ageing. CONCLUSION: A focus on the embodiment of vulnerability is a productive catalyst for research on the intimate connections between self and society, biology and culture, and reason and emotion. Such a research agenda would be the hallmark of a holistic approach to the arts and nursing.     

Ageing and free radicals.

Mammalian ageing is a universal phenomenon that is both obvious and inevitable, yet poorly understood, and under-researched at the molecular level. Numerous ageing theories have been proposed to explain the progressive and deleterious changes characteristic of ageing. One of the most popular of these is the 'free radical' theory of ageing, which proposes that ageing results from imperfect protection against tissue damage brought about by free radicals. Oxygen free radicals are constantly produced during aerobic metabolism, and certainly provide a universal mechanism for oxidative damage. However, a major obstacle to acceptance of the theory has been the poor record of antioxidants in prolonging the lifespan of small animals. Many other variables, such as genetic factors, temperature, activity and nutrition can affect lifespan, making it a highly complex multi-factorial process.     

海岛中老年男性部分雄激素缺乏综合征的流行病学调查

目的了解海岛地区中老年男性部分雄激素缺乏综合征(PADAM)的患病情况。方法采用多级抽样的方法,选取舟山市定海区612例45岁以上中老年男性进行PADAM自我症状评定量和外周静脉血雄激素水平测定,根据相应判断依据进行PADAM的诊断并用二项分布原理进行人群患病率的估计,采用方差分析或卡方检验等方法比较不同年龄组间的差异。结果PADAM自我症状评定结果显示:中老年男性PADAM患病率为39.87%(95%CI:35.99%～43.75%),不同年龄组差别有统计学意义(P<0.05),且各类症状得分值均随年龄的增高而上升;激素水平测定结果显示:舟山海岛中老年男性PADAM患病率为30.72%(95%CI:27.06%～34.38%),除黄体生成素水平和性激素结合蛋白随年龄增加而升高外,总睾酮、游离睾酮、游离睾酮指数等均随着年龄的增加而下降。结论舟山海岛中老年人PADAM的患病率较高,各年龄组间存在差异,今后应进一步加强对PADAM的相关研究,为提高中老年男性的身心健康和改善生活质量提供科学的依据。     

Neuroinflammation and ageing: current theories and an overview of the data

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. This review will address the current understanding of the relationship between ageing and several factors both genetics and life style related. Firstly we focused on the most reliable and commonly shared theories which attempt to explain the phenomenon of ageing as the genetic, cellular, neuroendocrine, immunological and free-radicals related theories. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. In this review special attention was dedicated to diseases related to age as atherosclerosis, cancer and Alzheimer disease. Despite the fact that in recent years many theories about ageing have been developed, we are still far from a full understanding of the mechanisms underlying the ageing process.     

Mediators of Well‐being in Ageing Family Carers of Adults with Intellectual Disabilities

Background Increasing numbers of adults with an intellectual disability are being cared for at home by ageing parents. The purpose of this study was to determine whether carer resources (i.e. social support and formal service use) and carer appraisals of ageing and stress/burden mediate the relationships between (1) maladaptive behaviour and carer depression; (2) carer health and carer depression; (3) maladaptive behaviour and carer quality of life; and (4) carer health and carer quality of life. Methods Eighty parents over the age of 50 were interviewed using a number of measures concerning their overall health, perceptions of ageing and stress, depression, and their child's maladaptive behaviour. Results Carer perceptions of ageing and stress emerged as significant mediators of the relationship between carer health and depression. In addition, perceived carer stress emerged as a significant mediator of the relationship between maladaptive behaviour and carer depression. Resources and appraisals did not emerge as significant mediators in analyses using quality of life as a positive outcome. Conclusions Results highlight the important contributions of appraisals to well‐being and raise questions for future research regarding the role of resources such as informal and formal support in the coping process.