Network remodeling of intramural coronary resistance arteries in the aged rat: A statistical analysis of geometry

AimsTo identify the geometrical alterations in the age-remodeled rat coronary artery network and to develop a useful technique to analyze network properties in the rat heart.Methods and resultsWe analyzed the networks of the left anterior descendent coronary arteries on in situ perfused hearts of young (3 months) and old (18 months) male rats. All segments and branching over >80 μm diameter were analyzed using 50 μm long cylindrical ring units of the networks. Arterial widening and paucity, increased tortuosity were typical features in the old network. In addition, axis angles deviated more from the mother branches in the old, whereas the diameters of daughter branches fit the Murray law in both groups. The detected changes in the old network resulted in a longer blood flow route for the same direct distance.ConclusionWe developed a useful method to investigate arterial network property changes in the rat heart. Ageing resulted in longer, more tortuous flow route in the LAD network that might be hemodynamically disadvantageous.     

Growth Factors in Intervertebral Disc Homeostasis

Intervertebral disc degeneration is a complex age-related pathology associated with back pain. Research on the growth factors that regulate disc homeostasis is of critical importance for understanding the basis of the disease. Here we summarize the data on the expression and function of various growth factors in the disc from in vivo and in vitro studies, as well as on their alterations during degeneration and ageing. Such studies are becoming more crucial in the prospect of clinical application of growth factors for the treatment of disc degeneration.     

Towards measurement of the Healthy Ageing Phenotype in lifestyle-based intervention studies

Introduction

Given the biological complexity of the ageing process, there is no single, simple and reliable measure of how healthily someone is ageing. Intervention studies need a panel of measures which capture key features of healthy ageing. To help guide our research in this area, we have adopted the concept of the “Healthy Ageing Phenotype” (HAP) and this study aimed to (i) identify the most important features of the HAP and (ii) identify/develop tools for measurement of those features.

Methods

After a comprehensive assessment of the literature we selected the following domains: physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we hoped would provide a reasonably holistic characterisation of the HAP. We reviewed the literature and identified systematic reviews and/or meta-analysis of cohort studies, and clinical guidelines on outcome measures of these domains relevant to the HAP. Selection criteria for these measures included: frequent use in longitudinal studies of ageing; expected to change with age; evidence for strong association with/prediction of ageing-related phenotypes such as morbidity, mortality and lifespan; whenever possible, focus on studies measuring these outcomes in populations rather than on individuals selected on the basis of a particular disease; (bio)markers that respond to (lifestyle-based) intervention. Proposed markers were exposed to critique in a Workshop held in Newcastle, UK in October 2012.

Results

We have selected a tentative panel of (bio)markers of physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we propose may be useful in characterising the HAP and which may have utility as outcome measures in intervention studies. In addition, we have identified a number of tools which could be applied in community-based intervention studies designed to enhance healthy ageing.

Conclusions

We have proposed, tentatively, a panel of outcome measures which could be deployed in community-based, lifestyle intervention studies. The evidence base for selection of measurement domains is less well developed in some areas e.g. social wellbeing (where the definition of the concept itself remains elusive) and this has implications for the identification of appropriate tools. Although we have developed this panel as potential outcomes for intervention studies, we recognise that broader agreement on the concept of the HAP and on tools for its measurement could have wider utility and e.g. could facilitate comparisons of healthy ageing across diverse study designs and populations.     

Senescence in tissue samples of humans with age-related diseases: A systematic review

BackgroundHigher numbers of senescent cells have been implicated in age-related disease pathologies. However, whether different diseases have different senescent phenotypes is unknown. Here we provide a systematic overview of the current available evidence of senescent cells in age-related diseases pathologies in humans and the markers currently used to detect senescence levels in humans.MethodsPubMed, Web of Science and EMBASE were systematically searched from inception to the 29^th of September 2019, using keywords related to ‘senescence’, ‘age-related diseases’ and ‘biopsies’.ResultsIn total 12,590 articles were retrieved of which 103 articles were included in this review. The role of senescence in age-related disease has been assessed in 9 different human organ system and 27 different age-related diseases of which heart (27/103) and the respiratory systems (18/103) are the most investigated. Overall, 27 different markers of senescence have been used to determine cellular senescence and the cell cycle regulator p16^ink4a is most often used (23/27 age-related pathologies).ConclusionThis review demonstrates that a higher expression of senescence markers are observed within disease pathologies. However, not all markers to detect senescence have been assessed in all tissue types.     

Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline

In the United Kingdom (UK), it is projected that by 2035 people aged >65 years will make up 23 % of the population, with those aged >85 years accounting for 5% of the total population. Ageing is associated with progressive changes in muscle metabolism and a decline in functional capacity, leading to a loss of independence. Muscle metabolic changes associated with ageing have been linked to alterations in muscle architecture and declines in muscle mass and insulin sensitivity. However, the biological features often attributed to muscle ageing are also seen in controlled studies of physical inactivity (e.g. reduced step-count and bed-rest), and it is currently unclear how many of these ageing features are due to ageing per se or sedentarism. This is particularly relevant at a time of home confinements reducing physical activity levels during the Covid-19 pandemic. Current knowledge gaps include the relative contribution that physical inactivity plays in the development of many of the negative features associated with muscle decline in older age. Similarly, data demonstrating positive effects of government recommended physical activity guidelines on muscle health are largely non-existent. It is imperative therefore that research examining interactions between ageing, physical activity and muscle mass and metabolic health is prioritised so that it can inform on the “normal” muscle ageing process and on strategies for improving health span and well-being. This review will focus on important changes in muscle architecture and metabolism that accompany ageing and highlight the likely contribution of physical inactivity to these changes.     

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.     

In vitro characterisation of arterial stiffening: From the macro- to the nano-scale

Accurate measurement of the material properties of arterial tissue is important for better characterisation of diseases and the development of reliable computational models. There are a number of in vitro techniques that are applied to study the biomechanical properties of arterial tissue. This review article presents data obtained using tensile testing, nanoindentation, scanning acoustic microscopy (SAM) and atomic force microscopy (AFM). Each of these techniques provides material property information at a different spatial resolution and in many ways are complementary techniques. The lack of consensus in the literature with regard to the appropriate stress and strain definitions that should be used when reporting tensile testing data is also highlighted. The potential of higher spatial resolution techniques, which provide data at micro-scale (nanoindentation and SAM) and nano-scale (AFM) for application to the characterisation of human aortic tissue are discussed. Finally, studies, which have examined age-related changed in the aorta at these different length scales, are highlighted.     

Age and the architecture of oral mucosa

Age changes affect the oral mucosa (the protective lining of the oral cavity), but few of these have been studied objectively. The aim of this study was to quantitatively analyse a number of morphometric parameters of the ageing oral mucosa. The fractal dimension of the epithelial connective tissue interface (ECTI) was estimated in 42 samples of normal buccal mucosa to correlate any changes in their irregularity to the age of the individuals. Morphometric parameters extracted from theoretical cell areas computed programatically were also analysed. Results showed no significant change in ECTI complexity associated with age; however, there was indication that epithelial cells tended to become larger and flatter with age. Interestingly, while some parameters did not show significant differences case wise, cluster analysis showed that the data clustered the cases into three main age groups: one representing the first two decades of life, another group represents adult life (21–50 years) and the last group representing the ageing population (50–90 years).