Effects Of Age-related Changes Research Articles

Unlocking the Role of Age-Related Changes to Fibroblasts in Pancreatic Cancer.

Pancreatic cancer prevalence increases with age, and disease prognosis is poorer in older individuals. The increased prevalence is driven, undoubtedly, by the multistep accumulation of oncogenic mutations in cancer cells with age. However, fibroblasts are major constituents and key players in pancreatic cancer, and they too undergo age-related changes that may contribute to disease severity. In this issue of Cancer Research, Zabransky and colleagues set out to dissect the effect of age-related changes in pancreatic fibroblasts on pancreatic ductal adenocarcinoma growth and metastasis. They discovered that aged fibroblasts secrete GDF-15, which in turn activates AKT signaling and accelerates tumor progression. These findings provide a mechanistic role for aged fibroblasts in pancreatic cancer, underpinning the importance of normal physiologic processes in tumor progression. See related article by Zabransky et al., p. 1221.

Midlife Speech Perception Deficits: Impact of Extended High-Frequency Hearing, Peripheral Neural Function, and Cognitive Abilities.

The objectives of the present study were to investigate the effects of age-related changes in extended high-frequency (EHF) hearing, peripheral neural function, working memory, and executive function on speech perception deficits in middle-aged individuals with clinically normal hearing. We administered a comprehensive assessment battery to 37 participants spanning the age range of 20 to 56 years. This battery encompassed various evaluations, including standard and EHF pure-tone audiometry, ranging from 0.25 to 16 kHz. In addition, we conducted auditory brainstem response assessments with varying stimulation rates and levels, a spatial release from masking (SRM) task, and cognitive evaluations that involved the Trail Making test (TMT) for assessing executive function and the Abbreviated Reading Span test (ARST) for measuring working memory. The results indicated a decline in hearing sensitivities at EHFs and an increase in completion times for the TMT with age. In addition, as age increased, there was a corresponding decrease in the amount of SRM. The declines in SRM were associated with age-related declines in hearing sensitivity at EHFs and TMT performance. While we observed an age-related decline in wave I responses, this decline was primarily driven by age-related reductions in EHF thresholds. In addition, the results obtained using the ARST did not show an age-related decline. Neither the auditory brainstem response results nor ARST scores were correlated with the amount of SRM. These findings suggest that speech perception deficits in middle age are primarily linked to declines in EHF hearing and executive function, rather than cochlear synaptopathy or working memory.

Impact of Age-Related Change in Caval Flow Ratio on Hepatic Flow Distribution in the Fontan Circulation.

The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.

Abstract 161: Aged mice decelerate bone metastasis of prostate cancer by decreasing infiltration of M2 macrophages

Abstract Bone metastasis is a major contributor to the mortality of patients with prostate cancer and results in the development of an immunosuppressive microenvironment in the bone marrow. While advanced age increases the risk of bone metastasis, effects of age-related changes on immune microenvironmental homeostasis are not yet clearly understood. To investigate interactions between cancer cells and the immune microenvironment in elderly individuals, we utilized murine-derived specific bone metastatic prostate cancer cells (RM1-BM), which we had previously isolated from bone metastatic mice and transfected with a luciferase-based reporter gene. We then injected the cells into the left ventricle of both 3‒6 months and 22‒24 months, male, wild-type mice to induce bone metastasis, using age-matched mice injected with PBS as a control. We employed in vivo imaging to compare the metastatic levels in both groups of mice every other day. On day 14, we extracted bone marrow cells for CyTOF analysis and femurs and tibias for Hematoxylin and Eosin staining. Interestingly, our preliminary results demonstrated that healthy aged mice exhibited a lower susceptibility to develop bone metastasis when compared to their younger counterparts. A further investigation of the immune subtypes revealed an increase in the percentage of macrophages in CD45+ immune cells in young mice that developed bone metastasis as opposed to age-matched controls. However, the percentage decreased in aged mice, going from 12.20% to 9.92% (p = 0.001). Lastly, macrophages were isolated from the bone marrow of 3‒6 months and 22‒24 months old mice and were co-cultured with ovalbumin-transfected RM1-BM cells (RM1-BM-ova) in vitro for 24 hours. The flow cytometry results indicated that both groups consist mainly of CD206+ (M2) macrophages. Nonetheless, those obtained from aged mice exhibited reduced ovalbumin presentation capability while maintaining a steady level of type I major histocompatibility complex (MHC-I). These findings suggested that increased infiltration of pro-inflammatory M2 macrophages within the tumor microenvironment may contribute to the bone metastasis of prostate cancer. Therefore, inhibiting M2 macrophages recruitment to the bone marrow microenvironment may prove a useful approach for treating patients with prostate cancer bone metastasis. This study was supported by the NSFC projects (81972420, 81972766, 82173336), and grants from the Shenzhen Science and Technology Innovation Commission (JCYJ20190809161811237, JCYJ20210324104214040). Citation Format: Xiao Zhang, Wei Yu, Xin Huang, Yi Lu, Jian Zhang. Aged mice decelerate bone metastasis of prostate cancer by decreasing infiltration of M2 macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 161.

Investigation of the Effects of Age-Related Changes in the Vestibular System on Balance: A Review

The vestibular system (VS) undertakes vital tasks for the survival of the individual by perceiving the movement of the head according to gravity and adjusting on balance, autonomic function, spatial perception, and orientation. In addition to being the first system to develop in the intrauterine period, the VS continues to develop with childhood. Although the onset time varies depending on various factors, it is known that VS degenerates with aging. It has also been shown in the literature that the number of sensory vestibular hair cells decreases by approximately 6% per decade from birth to old age. In addition, neurons in the vestibular nuclei are known to decrease by about 3% per decade between the ages of 40 and 90. These age-related changes in VS may cause dizziness, loss of balance, unsteady gait, increased falls and even agitation, loneliness, and loss of self-confidence in elderly individuals. In addition, it is reported in the literature that falls due to vestibular disorder are among the third to tenth leading causes of death among older adults. In this sense, it is very important to determine age-related VS dysfunctions in the healthy aging action plans of the health systems of the countries and in the development of strategies to prevent age-related falls. At the same time, it is very valuable for physiotherapists working in the field of geriatric rehabilitation to know well the age-related changes of VS and its effects on balance in the creation of possible vestibular rehabilitation programs. We think that virtual reality applications applied in addition to vestibular rehabilitation for vestibular disorders are promising, especially hearing problems in the elderly population should not be overlooked and hearing aids should be prescribed if needed.

Longitudinal Changes in Neuropsychological Functioning in Japanese Patients with Myotonic Dystrophy Type 1: A Five Year Follow-Up Study.

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy that causes various symptoms, including those of the central nervous system. Some studies have reported cognitive decline in patients with DM1, although the available evidence is limited. This study aimed to describe longitudinal differences in neuropsychological function in patients with DM1. A total of 66 Japanese adult patients with DM1 were investigated using a neuropsychological battery to assess several cognitive domains, including memory, processing speed, and executive function. The patients underwent neuropsychological evaluation approximately five years after baseline (Times 1 and 2). Thirty-eight patients underwent a second neuropsychological evaluation. The participants in the Time 2 evaluation were younger than those who did not participate in Time 2. Patients showed a decline in the Mini-Mental State Examination, Trail Making Test (TMT), Block Design, and Symbol Digit Modalities Test at Time 2 (P < 0.05). Age at Time 1 was associated with a decline in TMT-A and TMT-B scores (rho = 0.57 and 0.45, respectively). These results suggest a cognitive decline in patients with DM1 and warrant further investigation into the possible effects of age-related changes.

ATAC-clock: An aging clock based on chromatin accessibility

The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks.

Bilateral Functional Electrical Stimulation for the Treatment of Presbyphonia in a Sheep Model.

The aim of the study was to increase muscle volume and improve phonation characteristics of the aged ovine larynx by functional electrical stimulation (FES) using a minimally invasive surgical procedure. Stimulation electrodes were placed bilaterally near the terminal adduction branch of the recurrent laryngeal nerves (RLN). The electrodes were connected to battery powered pulse generators implanted subcutaneously at the neck region. Training patterns were programmed by an external programmer using a bidirectional radio frequency link. Training sessions were repeated automatically by the implant every other day for 1 week followed by every day for 8 weeks in the awake animal. Another group of animals were used as sham, with electrodes positioned but not connected to an implant. Outcome parameters included gene expression analysis, histological assessment of muscle fiber size, functional analysis, and volumetric measurements based on three-dimensional reconstructions of the entire thyroarytenoid muscle (TAM). Increase in minimal muscle fiber diameter and an improvement in vocal efficiency were observed following FES, compared with sham animals. This is the first study to demonstrate beneficial effects in the TAM of FES at molecular, histological, and functional levels. FES of the terminal branches of the RLN reversed the effects of age-related changes and improved vocal efficiency. NA Laryngoscope, 134:848-854, 2024.

The importance of serial sarcomere addition for muscle function and the impact of aging.

During natural aging, skeletal muscle experiences impairments in mechanical performance due, in part, to changes in muscle architecture and size, notably with a loss of muscle cross-sectional area. Another important factor that has received less attention is the shortening of fascicle length, potentially reflective of a decrease in serial sarcomere number (SSN). Interventions that promote the growth of new serial sarcomeres, such as chronic stretching and eccentric-biased resistance training, have been suggested as potential ways to mitigate age-related impairments in muscle function. While current research suggests it is possible to stimulate serial sarcomerogenesis in muscle in old age, the magnitude of sarcomerogenesis may be less than in young muscle. This blunted effect may be partly due to age-related impairments in the pathways regulating mechanotransduction, muscle gene expression, and protein synthesis, as some have been implicated in SSN adaptation. The purpose of this review was to investigate the impact of aging on the ability for serial sarcomerogenesis, and elucidate the molecular pathways that may limit serial sarcomerogenesis in old age. Age-related changes in mTOR, IGF-1, myostatin, and serum response factor signalling, MuRFs, and satellite cells may hinder serial sarcomerogenesis. In addition, our current understanding of SSN in older humans is limited by assumptions based on ultrasound-derived fascicle length. Future research should explore the effects of age-related changes in the identified pathways on the ability to stimulate serial sarcomerogenesis, and better estimate SSN adaptations to gain a deeper understanding of the adaptability of muscle in old age.

Effect of Cell Age and Membrane Rigidity on Red Blood Cell Shape in Capillary Flow.

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear. In this study, we investigated the effect of RBC properties on the microcapillary in vitro flow behavior and their characteristic shapes in microfluidic channels. For this, we fractioned RBCs from healthy donors according to their age. Moreover, the membranes of fresh RBCs were chemically rigidified using diamide to study the effect of isolated graded-membrane rigidity. Our results show that a fraction of stable, asymmetric, off-centered slipper-like cells at high velocities decreases with increasing age or diamide concentration. However, while old cells form an enhanced number of stable symmetric croissants at the channel centerline, this shape class is suppressed for purely rigidified cells with diamide. Our study provides further knowledge about the distinct effects of age-related changes of intrinsic cell properties on the single-cell flow behavior of RBCs in confined flows due to inter-cellular age-related cell heterogeneity.

Effects of age-related changes in trunk and lower limb range of motion on gait

BackgroundThe ability to walk is crucial for maintaining independence and a high quality of life among older adults. Although gait characteristics have been extensively studied in older adults, most studies have investigated muscle activity in the joints of the trunk or the lower limbs without assessing their interactions. Thus, the causes of altered trunk and lower limb movement patterns in older adults remain to explore. Therefore, this study compared the joint kinematic parameters of both trunk and lower limbs between young and older adults to identify kinematic factors associated with changes in gait among older adults.MethodsIn total, 64 older (32 males, aged 68.34 ± 7.38 years; 32 females, aged 67.16 ± 6.66 years) and 64 young (32 males, aged 19.44 ± 0.84 years; 32 females, aged 19.69 ± 0.86 years) healthy adults participated in this study. The range of motion (ROM) of the thorax, pelvis, and trunk in the horizontal plane and of the hip, knee, and ankle joints of the lower limbs in the sagittal plane were measured using a motion capture system with wearable sensors. Two-way analysis of variance assessed differences in ROM by group, sex, and spatio-temporal gait parameters; Pearson correlation analysis assessed the correlation of the trunk and lower limbs.ResultsStep length, gait speed, and stride length were greater in young adults (p < 0.001) than in older adults, but older women displayed the fastest gait speed (p < 0.05). ROM values for the pelvis, thorax, trunk, knee joint, and ankle joint of young adults were greater (p < 0.05) than those in older adults. However, hip ROM in older adults was significantly greater than that in young adults (p < 0.05).ConclusionWith increasing age, ROM of the lower limbs, especially the ankle joint, decreased significantly, resulting in a significant decrease in gait speed. As ROM of the pelvis decreased, stride length decreased significantly in older adults, who compensate through thoracic rotation. Thus, older adults should enhance muscle strength and increase ROM to improve gait patterns.

Age-related Changes in Trigeminal Ganglion Macrophages Enhance Orofacial Ectopic Pain After Inferior Alveolar Nerve Injury.

The ectopic pain associated with inferior alveolar nerve (IAN) injury has been reported to involve macrophage expression in the trigeminal ganglion (TG). However, the effect of age-related changes on this abnormal pain conditions are still unknown. This study sought to clarify the involvement of age-related changes in macrophage expression and phenotypic conversion in the TG and how these changes enhance ectopic mechanical allodynia after IAN transection (IANX). We used senescence-accelerated mouse (SAM)-prone 8 (SAMP8) and SAM-resistance 1 (SAMR1) mice, which are commonly used to study ageing-related changes. Mechanical stimulation was applied to the whisker pad skin under light anaesthesia; the mechanical head withdrawal threshold (MHWT) was measured for 21 d post-IANX. We subsequently counted the numbers of Iba1 (macrophage marker)-immunoreactive (IR) cells, Iba1/CD11c (M1-like inflammatory macrophage marker)-co-IR cells, and Iba1/CD206 (M2-like anti-inflammatory macrophage marker)-co-IR cells in the TG innervating the whisker pad skin. After continuous intra-TG administration of liposomal clodronate Clophosome®-A (LCCA) to IANX-treated SAMP8-mice, the MHWT values of the whisker pad skin were examined. Five days post-IANX, the MHWT had significantly decreased in SAMP8 mice compared to SAMR1-mice. Iba1-IR and Iba1/CD11c-co-IR cell counts were significantly increased in SAMP8 mice compared to SAMR1 mice 5 d post-IANX. LCCA administration significantly restored MHWT compared to control-LCCA administration. Ectopic mechanical allodynia of whisker pad skin after IANX is exacerbated by ageing, which involves increases in M1-like inflammatory macrophages in the TG.

Takeover performance of older drivers in automated driving: A review

IntroductionThe introduction of automated vehicles to the road environment brings new challenges for older drivers. Level 3 of conditional automation requires drivers to take over control of their vehicle whenever the automated system reaches its limits. Even though autonomous vehicles may be of great benefit to older drivers in terms of safely maintaining their mobility, a better understanding of their takeover performance remains crucial. The objective of this review of the literature is to shed more light on the effects that aging has on takeover performance during automated driving. MethodsThree database searches were conducted: PsychINFO, Web Of Sciences, and TRID. Studies from the last decade which included groups of older drivers were reviewed. ResultsAfter checking through abstracts and texts of articles, 9 articles, 4 proceedings papers, and 1 technical report were included in this review. All studies included a driving simulator that refers to level 3 of automation (which requires supervision by the driver). Five out of fourteen studies showed that older adults had poorer takeover performance (in terms of takeover time and takeover quality) than younger adults. However, several factors, such as the type of non-driving related task (NDRT), were seen to influence takeover performance in older adults. Speed, type and duration of notification interval, distribution and duration of driving modes, and number of takeovers were all also factors of influence. ConclusionThis review synthesizes the results of 14 articles which investigate the effects of age-related changes on takeover performance. Various external factors as NDRTs, speed, type and duration of notification to take over, duration of the automated phase, distribution of the automated/manual phases may affect takeover performance in older adults. Even if the majority of articles showed that older adults are globally slower at taking over a vehicle than younger adults, findings concerning take over quality yield divergent results. It's probably due to age related cognitive changes, particularly in executive functions or to a great heterogeneity in this population. This literature review highlights the need to develop new research on the impact of aging on takeover performance.

The Prevalence and Characteristics of Diffuse Idiopathic Skeletal Hyperostosis (DISH): A Cross-Sectional Study of 1519 Japanese Individuals.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is a pathology characterized by enthesis ossification, but there have been few reports on epidemiological surveys. This report presents a cross-sectional survey of DISH from thoracic to sacral spine in patients at the tertiary emergency medical center. Methods: The patients were divided into DISH (+) group and DISH (−) group for a retrospective comparative study. The primary outcome measures were the frequency of DISH and the patient demographic data, the secondary outcome measures were the previous medical history (diabetes mellitus, cardiovascular disease), the extent of aortic calcification, the frequency of hyperostosis around the costovertebral joint and the mortality rate within 3 months of the initial examination. Results: This survey examined a total of 1519 patients. There were 265 cases (17.4%) in the DISH (+) group and 1254 cases in DISH (−) group. The prevalence of DISH was concentrated at the thoracolumbar junction, particularly at T9. The mean age, ratio of male and hyperostosis around the costovertebral joint were significantly higher in the DISH (+) group (p < 0.001), but there was no significant difference in other variables. Conclusions: The pathology of DISH might involve the effects of age-related changes or biomechanical effects.

Methodological issues in the observational studies conducted in older population: a narrative review

Introduction&#x0D; Well-conducted observational studies may represent valuable tools for getting insight to disease etiology, detecting the effect of age-related changes, and providing an important perspective on health risk factors and disabilities in an aging population. Nevertheless, this kind of research poses several challenges for researchers. The main aim of this narrative review was to address the potential methodological issues in performing the observational studies in the elderly, the factors that influence their participation, and the possible solutions for overcoming the barriers to research in this population.&#x0D; Methods&#x0D; Comprehensive search for the papers published in the period from January 1st 1980 until 31st July 2016 in English or Italian was conducted through MEDLINE, Scopus and Web of Science electronic databases. Findings from the included papers were finally summarized.&#x0D; Results&#x0D; In cohort studies, the following barriers were addressed: sample size calculation, ascertainment of the target population, frequency of data collection, exposure determination, multifactorial loss to follow-up (drop-outs), cognitive impairment, definition of confounders, and ethical aspects. Case-control studies were reported to be prone to the issues like ascertainment of cases and controls, willingness to participate, data accuracy, recall bias, issues related to patients’ multimorbidity, and cognitive impairment.&#x0D; Conclusions&#x0D; Important factors to consider in research in elderly people include: precise definition of the study population, well conducted recruitment process, engagement with family and home care staff, cognitive impairment assessment and the consequent relevant ethical and legal issues, relief of participant burden in order to minimize withdrawal, and engagement with the media.

Age-Related Differences in Transient Receptor Potential Vanilloid 1 and 2 Expression Patterns in the Trigeminal Ganglion Neurons Contribute to Changes in the Palatal Mucosal Heat Pain Sensitivity

Aging affects various sensory functions of the body. However, the effect on the oral mucosal nociception has remain unclear, so this elucidation is very important. Therefore, this study aimed to evaluate the effect of age-related changes in transient receptor potential vanilloid 1 (TRPV1) and TRPV2 expression in the trigeminal ganglion (TG) neurons on intraoral mucosal heat sensitivity in the senescence-accelerated mouse prone 8 (SAMP8) model. We used 23-week-old (aged) and 7-week-old (young) SAMP8 mice. Heat stimulation was applied to the palatal mucosa under light anesthesia; moreover, the heat head withdrawal threshold (HHWT) was measured. We counted the number of TRPV1-immunoreactive (IR) and TRPV2-IR TG neurons innervating the palatal mucosa. Additionally, we investigated changes in HHWT when TRPV1 or TRPV2 antagonists (SB366791 or Tranilast) were administered to the palatal mucosa. Aged SAMP8 mice showed a higher HHWT than young SAMP8 mice. Compared with the aged SAMP8 mice, young SAMP8 mice showed a larger number of TRPV1-IR small-diameter neurons and a smaller number of TRPV2-IR medium-sized neurons innervating the palatal mucosa. SB366791 administration increased the HHWT in young, but not aged SAMP8 mice. Contrastingly, Tranilast administration increased the HHWT in aged, but not young SAMP8 mice. These results suggest that the modulation of heat pain sensitivity in the oral mucosa due to aging is dependent on changes in the TRPV1 and TRPV2 expression patterns in the TG neurons innervating the palatal mucosa.

The effect of age-related changes on the toxicity of a dry extract of aerial part of chicory herb (Cichorium intybus L.)

The effect of age-related changes on the toxicity of a dry extract of aerial part of chicory herb (Cichorium intybus L.)

Reflectometry and molecular dynamics study of the impact of cholesterol and melatonin on model lipid membranes.

The effect of melatonin and/or cholesterol on the structural properties of a model lipid bilayer prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) has been investigated both experimentally and via molecular dynamics (MD) simulations. Neutron reflectometry experiments performed with single supported membranes revealed changes in lipid bilayer thickness upon the introduction of additional components. While the presence of cholesterol led to an increase in membrane thickness, the opposite effect was observed in the case of melatonin. The results obtained are in a good agreement with MD simulations which provided further information on the organization of components within the systems examined, indicating a mechanism underlying the membranes' thickness changes due to cholesterol and melatonin that had been observed experimentally. Cholesterol and melatonin preferentially accumulate in different membrane regions, presumably affecting the conformation of lipid hydrophobic moieties differently, and in turn having distinct impacts on the structure of the entire membrane. Our findings may be relevant for understanding the effects of age-related changes in cholesterol and melatonin concentrations, including thosein the brains of individuals with Alzheimer's disease.

Pharmacology, polypharmacy and the older adult: a review.

District nurses routinely visit and care for older patients who are prescribed multiple medicines. Older people living with multiple comorbidities and polypharmacy are commonly encountered in community nursing. It is important for nurses to recognise that regular medicines use and age-related physiological changes in older people place them at greater risk of medication-related harm. In order to understand this, an underpinning knowledge of the pharmacological principles relating to older people is required. This review will consider the effects of age-related changes and the impact of ageing on pharmacokinetics and pharmacodynamics. The relationship between polypharmacy and identifying high-risk drugs and adverse drug events will be explored. Medicines use in older adults with multimorbidity including frailty will be discussed. The role of district nurses in supporting older people with medicines optimisation will be considered, with a focus on how the community nurse can contribute to reducing avoidable harm for patients.

Effects of Aging on Impairment Ratings: Part 4: Musculoskeletal Issues

Abstract This article is the fourth of five in a series on the effects of age-related changes in impairment evaluations as defined by the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth and Sixth Editions. The present article addresses the musculoskeletal system and differs from the first three articles, which focused on apportionment of an impairment rating between aging and other causes. The medical literature supports the notion that age-related osteoarthritis (OA) changes in the hand and digits frequently are associated with injury and/or repetitive motion. Thus, apportionment is indicated, but deciding which came first, the imaging abnormality or the injury, requires consummate skill on behalf of the rating physician. OA also occurs in the knees and hips of older individuals. Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory disorder characterized by calcification and ossification of spinal ligaments and entheses and is unique, in the authors’ opinion, because of a positive correlation between aging and back pain caused by this condition. The article also addresses the association—or the lack thereof—between pathology and aging, as well as degenerative changes and symptoms, to facilitate causation analysis. For a fuller discussion of causation analysis for the spine, readers can consult the AMA Guides to the Evaluation of Disease and Injury Causation, Second Edition.