Skeletal muscle mass and body fat in relation to successful ageing of older adults: The multi-national MEDIS study

BackgroundThe determinants that promote successful ageing still remain unknown. The aim of the present work was to evaluate the role of skeletal muscle mass and body fat percentage (BF%), in the level of successful ageing.Methodsduring 2005–2011, 2663 older (aged 65–100 years) from 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the study. Appendicular skeletal muscle mass (ASM), skeletal muscle mass index (SMI) and BF% were calculated using population formulas. Dietary habits, energy intake, expenditure and energy balance were derived throughout standard procedures. A successful ageing index ranging from 0 to 10 was used.ResultsThe mean ASM mass was 24 ± 6.0 kg, the SMI was 0.84 ± 0.21 and the BF% was 44%. Females had lower SMI and higher BF% in comparison with males, respectively [(SMI: 0.66 ± 0.09 vs. 1.03 ± 0.11; BF%: 51% vs. 34%, (p < 0.001)]. High successful agers had better rates in ASM (p = 0.01), SMI (p < 0.001) and BF% (p < 0.001), compared with the medium and low successful ones. Changes in SMI [b-coefficient (95% CI):2.14 (1.57 to 2.71)] were positively associated with successful ageing, while changes in BF% [b-coefficient (95% CI): −0.04 (−0.05 to −0.03)] were inversely associated with successful ageing. Results from sensitivity analysis showed that the effects of variations on body composition were consistent, less pronounced in the positive energy balance group and more pronounced among the oldest old.ConclusionsBody composition changes seem to be associated with lower quality of life in the older adults, as measured through successful ageing.     

Molecular mechanisms and therapeutics of the deficit in specific force in ageing skeletal muscle

The age-related impairment in muscle force is only partially explained by the loss of muscle mass. The loss both in specific and absolute forces contributes to the muscle weakness measured in the elderly and in animal models of ageing. Successful interventions aimed at preventing age-associated functional deficits will require a better insight into the mechanisms underlying the decline in muscle-specific force. The present review article is focused on recent evidence supporting excitation-contraction uncoupling as a key factor underlying fast and slow muscle fiber impairment with ageing. The molecular, functional and structural factors supporting this theory and counteracting measures such as insulin-like growth factor 1 transgenic overexpression are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling

This paper examines two major possibilities for the striking loss of skeletal muscle mass and strength that occurs in very old animals and humans. It is concluded that muscle regeneration is not significantly impaired with age. Instead, it seems that individual myofibres undergo atrophy, with selective death of the fast type 2B myofibres, due to the combined effects of many age-related changes the main causes being: nutrition(under-nutrition and lack of vitamin D),decreased hormone levels (e.g growth hormone, testosterone), reduced physical activity, and a loss of nerves that innervate the muscles. The discussion focusses on the central role of a local muscle form of insulin-like growth factor-I (IGF-I) in muscle hypertrophy, atrophy and motor neurone loss. Reduced IGF-Isignalling is involved in muscle atrophy and results from decreased muscle exercise, reduced growth hormone and insulin levels, reduced vitamin D, and treatment with drugs like corticosteroids, dexamethasone, and cyclosporin. In addition, elevated levels of inflammatory cytokines like TNF-α and IL-6can cause muscle wasting (cachexia) although this is usually associated with disease, andTNF-α may also act (at least in part) by inhibiting IGF-I signalling. The possible clinical prevention of age-related muscle wasting (and associated motor neurone loss) by the locally acting muscle isoform of IGF-I is discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Successful ageing: The case of Taiwan

Aim: To investigate the conditions of successful ageing in Taiwan. Methods: The respondents included two age groups, namely, 45–64 years (n = 1143), and 65 years and older (n = 1309), from a cross‐section national representative survey conducted in 2007. Results: Older people faced more problems that cause depression than their counterparts. Eleven per cent of older people were in the labour market. Neither middle‐aged people nor older people were actively involved in volunteer services. Those who lived longer had less social support. Over 50% felt their financial preparations for later life were not adequate. Educational levels and family income were the significant factors affecting the levels of successful ageing. Conclusions: Improvement in the four dimensions of successful ageing must be re‐emphasised for both age groups.     

The anorexia of ageing

Ageing is associated with a reduction in appetite and food intake, which has been termed the `anorexia of ageing'. After age 70–75 years average body weight decreases, even in healthy people, disproportionately due to loss of lean tissue. The `physiological' anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition. Marked weight loss is common in the elderly and a major cause of morbidity and increased mortality. The cause(s) of the anorexia of ageing are largely unknown. We have identified several possibilities. Animal and preliminary human studies indicate that ageing is associated with increased satiety factors and a reduced feeding drive. Endogenous opioids stimulate eating. We administered iv infusions of the opioid antagonist naloxone to young and older adults. Overall, the suppression of food intake was not different in the two age groups, but was increased in older women, suggesting reduced stimulation of feeding by endogenous opioids in this group. Plasma concentrations of the satiety hormonecholecystokinin (CCK) increase with ageing. Intravenous CCK-8 infusion produced greater suppression of food intake in older than young subjects (33.5 vs 15.5% P = 0.026),indicating that sensitivity to the satiating effects of CCK is at least maintained and may increase withage. This raises the possibility of using CCK antagonists as stimulants of appetite and food intake in malnourished older people. This revised version was published online in July 2006 with corrections to the Cover Date.     

The uniqueness of subjective ageing: convergent and discriminant validity

Although a large body of research has demonstrated the predictive power of subjective ageing for several decisive developmental outcomes, there remains some controversy about whether subjective ageing truly represents a unique construct. Thus, information about the convergent and discriminant validity of different approaches to measuring subjective ageing is still critically needed. Using data from the 2014 wave of the German Ageing Survey, we examined how three established subjective ageing measures (subjective age, global attitude toward own ageing, multidimensional ageing-related cognitions) were inter-related as well as distinct from general dispositions (optimism, self-efficacy) and well-being (negative affect, depressive symptoms, self-rated health). Using correlational and multivariate regression analysis, we found that the three subjective ageing measures were significantly inter-related (r = |.09| to |.30|), and that each measure was distinct from general dispositions and well-being. The overlap with dispositional and well-being measures was lowest for subjective age and highest for global attitudes towards own ageing. The correlation between global attitudes towards own ageing and optimism was particularly striking. Despite the high convergent validity of the different dimensions of ageing cognitions, we nevertheless observed stronger associations between specific dimensions of ageing cognitions with negative affect and self-rated health. We conclude that researchers should be aware of the multidimensional nature of subjective ageing. Furthermore, subjective age appears to be a highly aggregated construct and future work is needed to clarify its correlates and reference points.Electronic supplementary materialThe online version of this article (10.1007/s10433-019-00529-7) contains supplementary material, which is available to authorized users.     

Neuroendocrine ageing

Abstract. Ageing is followed by an involution of neuroendocrine functions, resulting in a decreased secretion of sex steroids and growth hormone. In addition, Cortisol secretion may be inadequately elevated upon stress challenges, due to deficient braking functions by central glucocorticoid receptors. In combination, these endocrine perturbations will probably result in changes in psychological factors such as energy and well-being, altered body composition, and insulin resistance, as well as other risk factors for diseases characteristic of the ageing human, such as cardiovascular disease, non-insulin-dependent diabetes mellitus and stroke. This cluster of phenomena is frequently seen before the period of normal ageing, indicating premature ageing processes. The background factors in these conditions probably include psychosocial stressors, which are perceived differently depending on individual coping abilities. Socio-economic and other environmental factors, such as smoking and alcohol abuse, may well be responsible for the expression of this syndrome of premature ageing. Preventive and therapeutic trials with hormonal substitution therapy to treat these aberrations have been promising, and encourage further studies aimed at elucidating potential risks in relation to potential improvement of quality of life and, perhaps, longevity.     

The assessment of views on ageing: a review of self-report measures and innovative extensions

This is a review of existing self-report measures for assessing views on ageing. It provides an overview of instruments, for which basic psychometric properties are available and describes them according to the purposes for which they are suitable. Literature search resulted in the inclusion of 89 instruments which were categorised along eight dimensions. The majority of measures focus on explicit cognitions about people’s own age and ageing or other (older) people. A substantial amount of tools account for the multidimensionality and multidirectionality of views on ageing, i.e. the idea that ageing is accompanied by both gains and losses in several different domains. To some extent, measures reflect that ageing is a long-term process and that views on ageing are malleable, rather than just stable traits. Cluster analysis revealed heterogeneity in instruments regarding the dimensions of Ecosystem, Balance, Stability, Dynamics, and Complexity. It becomes apparent, however, that approaches to measure views on ageing should be extended to more specifically target the implicit level as well as affective, physiological, and behavioural manifestations. Additionally, means for capturing views on ageing on the societal level and tools with a distinct time reference are needed. This is particularly important when one wants to account for the lifelong dynamics of views on ageing.     

Views on ageing: a lifespan perspective

Views on ageing (VoA) have special relevance for the ageing process by influencing health, well-being, and longevity. Although VoA form early in life, so far, most research has concentrated on how VoA affect later middle-aged and older adults. In this theoretical article, we argue that a lifespan approach is needed in order to more fully understand the origins of VoA, how they change over ontogenetic time, and how they shape development across the full breadth of the lifespan. We begin by explicitly linking VoA to fundamental principles of lifespan development. We review existing theories of VoA and discuss their respective contributions and limitations. We then outline a lifespan approach to VoA that integrates existing theories and addresses some of their limitations. We elaborate on three core propositions of a lifespan approach to VoA: (1) VoA develop as the result of a dynamic, ongoing, and complex interaction between biological-evolutionary, psychological, and social-contextual factors; however, the relative importance of different sources changes across the lifespan; (2) VoA impact development across the whole lifespan; however, different outcomes, mechanisms, and time frames need to be considered in order to describe and understand their effects; and (3) VoA are multidimensional, multidirectional, and multifunctional throughout life, but their complexity, meaning, and adaptivity change across the lifespan. We conclude with recommendations for future lifespan research on VoA.     

The importance of cognitive ageing for understanding dementia

A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well-targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and starting earlier in the life course would allow the sources of variability in ageing to be better understood.     

尿液蛋白质组学与糖尿病肾病

蛋白质组学是系统研究细胞或组织全套蛋白质生物学信息的科学,其中尿液蛋白质组学以其独特的优点广泛应用于基础和临床研究领域.糖尿病肾病是糖尿病最常见且危害巨大的并发症之一,许多学者运用尿液蛋白质组学分析方法对糖尿病肾病进行研究,发现了一些与糖尿病肾病相关的生物学标志及可能的发生机制,展示了尿液蛋白质组学技术在糖尿病肾病早期诊断、动态监测病情及发现新的治疗靶点方面的前景.     

Shifting self-perceptions of ageing: differential effects of value priorities on self-perceptions of ageing beyond age stereotypes

Self-perceptions of ageing (SPA) are important predictors of health in later life. However, research on antecedents of SPA other than age stereotypes is scarce. To address this gap, this study investigates the impact of personal value priorities beyond age stereotypes on SPA. Can values as the motivational basis of attitudes and evaluations predict gain- and loss-related SPA? To answer this question, we conducted multiple regression analyses of longitudinal data from two waves (2008, 2011) of the German Ageing Survey (DEAS; N = 6089, age range in 2008: 40–93 years). Gain- and loss-related SPA as well as age stereotypes were assessed with two AgeCog scales and personal values with the 21-item Portrait Values Questionnaire. Results indicate that value priorities relate to SPA longitudinally in domain-specific ways: People with a value priority of openness to change and self-transcendence reported more gain-related SPA at follow-up, whereas those who prioritized conservation reported less gain-related SPA. In the domain of loss-related SPA, those people with a value priority of self-enhancement reported more and those prioritizing self-transcendence reported less loss-related SPA at follow-up. These results complement and extend recent findings on the role of personality for SPA. They suggest that whether people focus on the gains or losses that occur with age, whether they perceive ageing as a threat or chance, is not only shaped by their age stereotypes, but also by what they find important—their values.     

The Gompertz function does not measure ageing

The Gompertz transform of the distribution function for the age at death expresses mortality in a form R = R₀e^{alpha t} where R₀ is themortality at time zero and is the rate of increase ofmortality, frequently taken as the rate of ageing. The slope ofthe line is frequently used as a measure of the rate of ageing.It is argued that it is incorrect to use in this way. Tosupport this contention, a paradox is produced whereby selectionfor longevity increases , which could lead to the absurdconclusion that selection for longevity increases the rate ofageing.     

Haemophilia and ageing

Advances in the development of effective and safe treatments for haemophilia over the last 50 years have resulted in a significant increase in the life expectancy of persons with haemophilia (PWH). The management of this new cohort of middle-aged and elderly PWH is challenging because of the opposing risks of haemophilia and age-related cardiovascular disease and malignancy. Furthermore, this cohort of ageing PWH has the additional comorbidities of human immunodeficiency virus/hepatitis C and chronic haemophilic arthropathy. This article reviews the prevalence, underlying mechanisms and treatment strategies for managing these comorbidities. International collaboration is essential for registry data and further prospective trials to inform optimal evidence-based management for this rare disorder in the future.     

Subcellular distribution of GLUT 4 in the skeletal muscle of lean type 2 (non-insulin-dependent) diabetic patients in the basal state

Summary Insulin resistance of the skeletal muscle is a key feature of Type 2 (non-insulin-dependent) diabetes mellitus. To determine whether a decrease of glucose carrier proteins or an altered subcellular distribution of glucose transporters might contribute to the pathogenesis of the insulin resistant state, we measured glucose transporter numbers in membrane fractions of gastrocnemius muscle of 14 Type 2 diabetic patients and 16 non-diabetic control subjects under basal conditions. Cytochalasin-B binding and immunoblotting with antibodies against transporter-subtypes GLUT 1 and GLUT 4 were applied. The cytochalasin-B binding values (pmol binding sites/g muscle) found in a plasma membrane enriched fraction, high and low density membranes of both groups (diabetic patients and non-diabetic control subjects) suggested a reduced number of glucose transporters in the plasma membranes of the diabetic patients compared to the control subjects (diabetic patients: 1.47 ± 1.01, control subjects: 3.61 ± 2.29,p ≤ 0.003). There was no clear difference in cytochalasin-B binding sites in high and low density membranes of both groups (diabetic patients: high density membranes 3.76 ± 1.82, low density membranes: 1.67 ± 0.81; control subjects: high density membranes 5.09 ± 1.68, low density membranes 1.45 ± 0.90). By Western blotting analysis we determined the distribution of the glucose transporter sub-types GLUT 1 and GLUT 4 in the plasma membrane enriched fraction and low density membranes of seven patients of each group. In agreement with the cytochalasin-B binding data and despite a high variance within one group, the results show a clear decrease of GLUT 4 in the plasma membrane enriched fraction of diabetic patients compared to control subjects. In contrast, we found no difference in the distribution of GLUT 1 in diabetic patients and control subjects. In conclusion, despite a high variance of glucose transporter numbers in the skeletal muscle of different individuals fractionation of muscle samples clearly suggests that the number of GLUT 4 is reduced in the plasma membrane fraction of skeletal muscle of lean diabetic patients in the basal state.     

Genetics and proteomics of pituitary tumors

Genetics and proteomics determine structure and function of normal tissues, and the molecular alterations that underlie tumorigenesis result in changes in these aspects of tissue biology in neoplasms. We review the known genetic alterations in pituitary tumors. These include the oncogenic Gsα protein (GSP)-activating mutations, and pituitary tumor-derived fibroblast growth factor receptor-4 (ptd-FGFR4), as well as tumor suppressor gene mutations associated with multiple endocrine neoplasia type 1 (MEN1). Other candidates identified from expression profiling include pituitary tumor-transforming gene (PTTG), GADD45, and bone morphogenic protein (BMP)4. Proteomic changes in pituitary tumors include classical alterations identified by immunohistochemistry as well as epigenetic reductions in p27. The underlying mechanisms for dysregulated cell adhesive molecules including cadherins and FGFRs are reviewed. The combined use of genetic and proteomic approaches will enhance novel drug therapeutic development.     

Haemophilia and ageing

Summary.  Men with haemophilia have not only the challenges of living with HIV and/or HCV infection and premature arthritis as complications of their disorder, but they also confront the other ails of ageing. These include genitourinary problems such as prostatic hypertrophy, prostatic cancer and renal stone disease, and arterial disease for which haemophilia is not protective. Progressive arthritis and declining fitness may lead to loss of independence which causes great concern. Associated with the physical aspects of ageing, many patients also suffer from psychological symptoms which may be precipitated by changes in work such as early retirement and altered family dynamics. Many older men with haemophilia may never have consulted primary care physicians because of the rarity and complexity of their disorder. Haemophilia centre staff often assume responsibility for the identification and management of all health problems of their patients. Even when other clinicians are involved, patients require their centre's involvement in the investigation and support of many procedures such as coronary artery surgery and urological surgery. This paper addresses falls in the older man with haemophilia, their causes and consequences and cardiovascular problems in particular. Very little literature has been published about these common problems. We need to be aware of the ageing issues in haemophilia and develop 'wellness' programs which are directed to the early identification of disease as well as preventative strategies to reduce the physical and psychological impacts of ageing.     

Understanding ageing from an evolutionary perspective

There is clear heritability of human longevity. However, the genetics of ageing is likely to be complex. Evolution theory tells us not to expect genes that have been selected to promote ageing. Ageing is not programmed but results from accumulation of somatic damage, owing to limited investments in maintenance and repair. Genes controlling the levels of activities, such as DNA repair and antioxidant defence, thus regulate longevity. In addition, there may be contributions either from late-acting deleterious genes that escape the force of natural selection or that trade benefit at an early age against harm at older ages. In some species, there is evidence that genes have evolved to detect and respond to changes in the environment, e.g. food supply. Evolutionary understanding can also help to understand important features of the human life history such as menopause.