The effect of ageing on in vivo human ciliary muscle morphology and contractility

Purpose. To assess the effect of ageing on in vivo human ciliary muscle morphology and contractility during accommodation. Methods. Seventy-nine subjects, aged 19–70 years were recruited. High-resolution images were acquired of nasal and temporal ciliary muscle in the relaxed state, and at stimulus vergence levels of -4 and -8 D, using anterior segment optical coherence tomography (AS-OCT). Objective refractions and axial lengths were also recorded. Linear regression analysis was performed to determine the effect of age on nasal and temporal ciliary muscle morphologic characteristics. Results. Ciliary muscle anterior length decreased significantly with age both nasally (R = 0.461, P = 0.001) and temporally (R = 0.619, P < 0.001) in emmetropic eyes. In a subset of 37 participants, ciliary muscle maximum width increased significantly with age, by 2.8 µm/year nasally (R = 0.54, P < 0.001) and 3.0 µm/year temporally (R = 0.44, P = 0.007), while the distance from the inner apex of the ciliary muscle to the scleral spur decreased significantly with age on both the nasal and temporal aspects (R = 0.47; P = 0.004 and R = 0.43; P = 0.009, respectively). During accommodation, changes to ciliary muscle thickness and length remained constant throughout life. Conclusions. The human ciliary muscle undergoes age-dependent changes in morphology that suggest an antero-inwards displacement of muscle mass, particularly in emmetropic eyes. However, the morphologic changes observed appear not to affect the ability of the muscle to contract during accommodation, even in established presbyopes, thus supporting a lenticular model of presbyopia development.

The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens

The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.

Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA)

Introduction Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. Aim To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Methods Literature review and consensus of expert opinion. Results and conclusion MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach.

Ocular and systemic vascular function in human ageing

The importance of vascular risk factors in various age-related pathologies has been extensively researched. Nevertheless, the haemodynamic disturbance occurring in various ocular and systemic vascular beds to impact upon ocular function remained largely unknown. The purpose of the following studies was to explore the presence and impact of both ocular and systemic vascular dysregulation as well as biochemical vascular risk factors in healthy elderly individuals and patients with age-related macular degeneration. Furthermore, the possible role was played by circulatory oxidative stress and its relationship with endothelial dysfunction at both ocular and systemic levels has also been investigated. There were four principal sections to the present work: 1. To assess the relationship between ocular and systemic anti-oxidative defence in healthy individuals The principal findings of this work were: -It has been shown that MPOD significantly and positively related with circulatory GSH levels. 2. To investigate macro- and microcirculation and oxidative stress in early AMD patients without overt systemic disease The principal findings of this work were: -AMD patients exhibit abnormal macrocirculation compared to the controls. -Blood GSSG level was significantly higher in early AMD patients than controls. -AMD patients showed abnormal microcirculation at retinal level compared. -In early AMD patients, retinal venous RT positively correlated with blood GSSG levels. 3. To assess the relationship between ocular vascular function and circulatory markers of endothelial dysfunction and CVD risk The principal findings of this work were: -Age had a positive effect on ET-1, vWF and slope of retinal arterial constriction in otherwise healthy individuals. -Even in otherwise healthy individuals, retinal arterial vascular function showed a significant correlation with circulatory markers of endothelial dysfunction and CVD risk. 4. To assess age-related changes in ANS and vascular function, and their relationship to retinal vascular function parameters The principal findings of this work were: -Elderly individuals demonstrated abnormal circadian changes of PSNS activity compared to middle-aged group. -Elderly groups showed higher ET-1 and vWF level as well as C-IMT and AIx, and also impaired retinal vascular function compared to the middle-aged group. -In the elderly group, impaired retinal vascular function significantly correlated with the dysregulation of PSNS activity.

Free radicals and redox signalling in T-cells during chronic inflammation and ageing

During chronic inflammation and ageing, the increase in oxidative stress in both intracellular and extracellular compartments is likely to influence local cell functions. Redox changes alter the T-cell proteome in a quantitative and qualitative manner, and post-translational modifications to surface and cytoplasmic proteins by increased reactive species can influence T-cell function. Previously, we have shown that RA (rheumatoid arthritis) T-cells exhibit reduced ROS (reactive oxygen species) production in response to extracellular stimulation compared with age-matched controls, and basal ROS levels [measured as DCF (2',7'-dichlorofluorescein) fluorescence] are lower in RA T-cells. In contrast, exposing T-cells in vitro to different extracellular redox environments modulates intracellular signalling and enhances cytokine secretion. Together, these data suggest that a complex relationship exists between intra- and extra-cellular redox compartments which contribute to the T-cell phenotype.

The fatigue ageing of vulcanised rubbers

The cause of the respective rough and smooth fatigue failure surfaces of Neoprene GS : Neoprene W and Neoprene GS : natural rubber vulcanisates is investigated. The contrasting morphology of the vulcanisates is found to be the major factor determining the fatigue behaviour of the blends. Neoprene GS and Neoprene W appear to form homogeneous blends which exhibit physical properties and fatigue failure surfaces intermediate between those of the two horropolymers. Neoprene GS and natural rubber exhibit heterogeneity when blended together. The morphology of these blends is found to influence both the fatigue resistance and failure surface of the vulcanisates. Exceptional uncut and cut initiated fatigue lives are observed for blends having an interconnecting network morphology. The network structure and cross-link density of the elastomers in the blends and the addition of carbon black and antioxidant are all found to influence the fatigue resistance but not the failure mechanism of the vulcanisate.

A techno-economic study of the recycling of mixed plastics to useful products

The techno-economic implications of recycling the components of mixed plastics waste have been studied in a two-part investigation: (a) An economic survey of the prospects for plastics recycling, the plastics waste arisings from retailing, building, automotive, light engineering and chemical industries have been surveyed by mans of questionnaires and interviews. This was partially successful and indicated that very considerable quantities of relatively clean plastics packaging was available in major department chains and household stores. The possibility of devising collection systems for such sources, which do not lead to any extra cost, have been suggested. However, the household collection of plastics waste has been found to be uneconomic due to high cost of collection, transportation and lack of markets for the end products. (b) In a technical study of blends of PE/PP and PE/PS which are found in admixture in waste plastics, it has been shown that they exhibit poor mechanical properties due to incompatibility. Consequently reprocessing of such unsegregated blends results in products of little technological value. The inclusion of some commercial block and graft copolymers which behave as solid phase dispersants (SPES) increase the toughness of the blends (e.g. EPDM in PE/PP blend and SBS in PE/PS blend). Also, EPDM is found to be very effective for improving the toughness of single component polypropylene. However, the improved Technical properties of such blends have been accompanied by a fast rate of photo-oxidation and loss of toughness due to the presence of unsaturation in SPD's. The change in mechanical properties occurring during oven ageing and ultra-violet light accelerated weathering of these binary and ternary blends was followed by a viscoelastonetric technique (Rheovibron) over 9,, wide range of temperatures, impact resistance at room temperature (20-41'G) and changes in functional groups (i.e. carbonyl and trans-1,4-polybutadiene). Also the heat and light stability of single and mixed plastics to which thiol antioxidants were bound to SPE1 segment have been studied and compared with conventional antioxidants. The long-term performance of the mixed plastics containing SPE1 have been improved significantly by the use of conventional and bound antioxidants. It is concluded that an estimated amount of 30000 tonnes/year of plastics waste is available from department chains and household stores which can be converted to useful end products. This justifies pilot-experiments in collaboration with supermarkets, recyclers and converters by use of low cost SPD's and additives designed to make the materials more compatible.

The impact of ageing on the barriers to drug delivery

Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery. © 2012 Elsevier B.V. All rights reserved.

Dimensional changes in the ageing cornea

The study investigated the central and peripheral corneal characteristics of groups of subjects from 20 to 90 years of age to assist the understanding of ageing changes in the cornea, and to see whether relationships between ocular parameters were revealed. After age 45 the corneal horizontal radius of curvature gradually decreased with age. This trend was shown by the Aston University subjects (group B). The effect was very significant for the hospital patients undergoing biometry before cataract extraction operation (group D). Vertical radius of curvature showed a slight decrease with age after age 45, but similar to corneal eccentricity, this showed no significant age effect. Corneal astigmatism progressed from with the rule towards against the rule, particularly after age 60. The shift seemed mainly due to the decreasing horizontal corneal curvature. In biometry no significant age relation was found for axial length, but a significant relation was found between curvature and axial length in the larger group D. Lens thickness showed a very significant relation to age and to axial length, but no significant relation to corneal curvature. Anterior chamber depth showed a very significant relation to age, lens thickness and axial length, but no significant relation to corneal curvature. A significant age effect was found for corneal thickness decreasing with age for the central, nasal and temporal regions of the right eye. Analysis of the biometry results indicated the influence of two major factors. Firstly, the natural growth of the eye in youth, leading to greater values of axial length, radius of corneal curvature, lens thickness and anterior chamber depth. Secondly, the typical ageing changes where the increasing lens thickness caused a reduction in anterior chamber depth. The decrease in corneal thickness with age shown in some corneal regions may be a sign of ageing changes in the tissue proteins and hydration balance.

Anticholinergic medication use and cognitive impairment in the older population:the Medical Research Council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=-0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.