Search

BackgroundRestraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.MethodsUsing Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.ResultsWe developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.ConclusionsOur method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patients directives, family feelings and representatives desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Human-animal relationships are vital for many older persons. Finding ways to include animals in aged care settings can be part of reorienting aged care settings from a solely humancentric focus to a human-animal inclusive one for the 21st century. This case study project report describes the development of an animal inclusive model of care for a Residential Aged Care Facility (RACF) in a regional town in Australia. The model’s primary objective was to facilitate residents’ empowerment through safe engagements with animals as a source of health and wellbeing while incorporating best practise animal-care and husbandry. Exemplars used to inform the model included The Eden AlternativeTM and Care Farms. The Sanctuary model sought to cover several gaps identified in these approaches. These included clear policies and protocols regarding animal welfare, infrastructure needs (animal housing and designated human-animal interaction areas), staffing models, stakeholder engagement approaches (both within the RACF and the local community) and developing sustainable resourcing and financial frameworks. A vision to establish a refuge for both humans and animals was inherent in the design of the Sanctuary model, and to operationalize this vision, policies, resourcing plans and practical processes were formulated informed by multi-species ethical understandings. Regrettably, it was not possible to fully implement the model. However, this case study is presented with the aim of seeking to redress the noted 85% wastage of global health research; a wastage that includes human-animal research knowledge. Insights into opportunities and barriers and experiential knowledge are shared with the aim of facilitating future endeavours to implement parallel visions that embed human and animal inclusive models in residential aged care in the future.

Background: Ageing is associated with an increased risk of lung infection and chronic inflammatory lung disease. Innate immune responses are the first line of defence in the respiratory tract, however, age-related changes to innate immunity in the lung are not fully described. Both resident haematopoietic cells, such as alveolar macrophages, and non-haematopoeitic cells, such as epithelial and endothelial cells can contribute to inflammatory and immune responses in the lung. In this study we aimed to determine the impact of ageing on early innate responses of resident cells in the lung. Results: Aged and young mice were inoculated intranasally with lipopolysaccharide (LPS). After 4 h, aged mice recruited higher numbers of neutrophils to the airways and lung. This exacerbated inflammatory response was associated with higher concentrations of chemokines CXCL1, CXCL2 and CCL2 in the airways. Next, precision cut lung slices (PCLS) were stimulated ex vivo with LPS for 16 h. Gene expression of Cxcl2, Tnf and Il1b were all higher in PCLS from aged than young mice and higher levels of secretion of CXCL2 and TNF were detected. To determine which lung cells were altered by age, LPS was intranasally administered to aged and young mice and individual populations of cells isolated by FACS. RT-PCR on sorted cell populations demonstrated higher expression of inflammatory cytokines Cxcl2, Ccl2 and Tnf in epithelial cells and alveolar macrophages and higher expression of Cxcl2 by endothelial cells of aged mice compared to young. These differences in expression of pro-inflammatory cytokines did not correspond to higher levels of Tlr4 expression. Conclusions: Ageing leads to a heightened neutrophilic inflammatory response in the lung after LPS exposure, and higher expression and production of pro-inflammatory cytokines by resident lung cells, including alveolar macrophages, epithelial cells and endothelial cells. The responses of multiple resident lung cell populations are altered by aging and contribute to the exacerbated inflammation in the lung following LPS challenge. This has implications for our understanding of respiratory infections and inflammation in older people. [ABSTRACT FROM AUTHOR]

Background: Few studies have quantified multimorbidity and frailty trends within hospital settings, with even fewer reporting how much is attributable to the ageing population and individual patient factors. Studies to date have tended to focus on people over 65, rarely capturing older people or stratifying findings by planned and unplanned activity. As the UK's national health service (NHS) backlog worsens, and debates about productivity dominate, it is essential to understand these hospital trends so health services can meet them. Methods: Hospital Episode Statistics inpatient admission records were extracted for adults between 2006 and 2021. Multimorbidity and frailty was measured using Elixhauser Comorbidity Index and Soong Frailty Scores. Yearly proportions of people with Elixhauser conditions (0, 1, 2, 3 +) or frailty syndromes (0, 1, 2 +) were reported, and the prevalence between 2006 and 2021 compared. Logistic regression models measured how much patient factors impacted the likelihood of having three or more Elixhauser conditions or two or more frailty syndromes. Results were stratified by age groups (18–44, 45–64 and 65 +) and admission type (emergency or elective). Results: The study included 107 million adult inpatient hospital episodes. Overall, the proportion of admissions with one or more Elixhauser conditions rose for acute and elective admissions, with the trend becoming more prominent as age increased. This was most striking among acute admissions for people aged 65 and over, who saw a 35.2% absolute increase in the proportion of admissions who had three or more Elixhauser conditions. This means there were 915,221 extra hospital episodes in the last 12 months of the study, by people who had at least three Elixhauser conditions compared with 15 years ago. The findings were similar for people who had one or more frailty syndromes. Overall, year, age and socioeconomic deprivation were found to be strongly and positively associated with having three or more Elixhauser conditions or two or more frailty syndromes, with socioeconomic deprivation showing a strong dose–response relationship. Conclusions: Overall, the proportion of hospital admissions with multiple conditions or frailty syndromes has risen over the last 15 years. This matches smaller-scale and anecdotal reports from hospitals and can inform how hospitals are reimbursed. [ABSTRACT FROM AUTHOR]

Methods: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. Results: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. Discussion: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slowwave sleep and long-term memory may have clinical implications. [ABSTRACT FROM AUTHOR]

Age‐related hearing impairment (ARHI) is commonly associated with decreased auditory temporal resolution caused by auditory neurodegeneration. Age‐related deterioration in gap detection ability, resulting in poor temporal auditory processing, is often attributed to pathophysiological changes in both the peripheral and central auditory systems. This study aimed to investigate whether the gap detection ability declines in the early stages of ageing and to determine its usefulness in detecting peripheral and central auditory degeneration. The study used 1‐month‐old (1 M), 6‐month‐old (6 M) and 12‐month‐old (12 M) mice to examine changes in gap detection ability and associated auditory pathophysiology. Although hearing thresholds did not significantly differ between the groups, the amplitude of auditory brainstem response (ABR) wave I decreased significantly in an age‐dependent manner, consistent with age‐related cochlear synaptopathy. The relative ABR amplitude ratio of waves 2 and 5 to wave 1 was significantly increased in 12 M mice, indicating that the central auditory system had increased in relative neuroactivity. A significant increase in gap detection thresholds was observed in 12 M mice compared to 1 M mice. Although cochlear synaptopathy and central hyperactivity were positively correlated with gap detection thresholds, central hyperactivity strongly influenced gap detection ability. In the cochlear nucleus and auditory cortex, the inhibitory synaptic expression of GAD65 and the expression of parvalbumin were significantly decreased in 12 M mice, consistent with central hyperactivity. Evaluating gap detection performance may allow the identification of decreased auditory temporal resolution in the early stages of ARHI, which is strongly associated with auditory neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: The population in Latin America and Caribbean (LAC) has experienced a major demographic transition with increased numbers of older adults (OA). This change brings opportunities in the public health sector to implement health prevention interventions and delay the onset of geriatric syndromes. Micronutrients play an important role in the maintenance of biological function which contributes to longevity. Micronutrient deficiencies (MD) in OA increase the risk for onset of chronic comorbidities and geriatric syndromes. Aim: To review and summarize the existing data on micronutrient status in OA in the LAC region and discuss the gaps and challenges in public health approaches to address deficiencies. Methods: Literature review in Medline for records describing nutritional biomarkers in older adults (≥ 60y) from community dwelling and population-based studies in LAC. Results: Few countries (including Chile, Ecuador, Costa Rica, Brazil, and Mexico) have documented one or more nutritional deficiencies for OA in national health surveys, however across the entire region, evidence of micronutrient levels is scarce. Some surveys have documented a high prevalence and large heterogeneity in the prevalence of vitamin D followed by B12 deficiency, being the 2 MDs most studied due their effects on cognition, frailty, and bone mineral density in the OA population. Other MD including C, E, A, copper, zinc, iron, and selenium have also been reported. Conclusion: Information on the micronutrient status in OA from LAC is poorly documented. Research and capacity building initiatives in the region are crucial to develop tailored strategies that address the specific nutritional needs and challenges faced by the ageing population in Latin America. Plain language title: Micronutrients Deficiencies in Older Adults in Latin American Plain language summary: For the first time, there are more older adults (OA) than children worldwide. In the Latin America and Caribbean (LAC) region, OA represents 13.2% of the population, and it is projected to increase to 30% (220 millions) by 2030. This demographic shift represents an opportunity in the public health sector to implement health prevention strategies and public health policies to delay the onset of geriatric syndromes in the younger generation. Vitamins and minerals (micronutrients) are necessary in our body to maintain biological function. Deficiencies in older ages have been associated with the onset of geriatric syndromes (such as sarcopenia, frailty, cognitive impairment, and falls, among others). Therefore, it is relevant to understand the magnitude and distribution of micronutrient deficiencies in OA in the LAC region. This will help to inform decision-makers to further implement early actions to maintain good nutrition and health status in the population. In this narrative review, we highlight that few countries in the LAC region documented one or more nutritional deficiencies for OA in their national health surveys. Across the entire region, evidence of micronutrient levels in OA is scarce. Vitamin D and vitamin B12 are the 2 most reported micronutrients in the OA population. Research and capacity-building in the region are crucial to develop tailored strategies to address specific nutritional needs and challenges faced by the aging population in Latin America. [ABSTRACT FROM AUTHOR]

Due to the limitations imposed by urban power grid outages for maintenance, on‐line harmonic current detection technology for distribution network cables is expected to become an effective supplement to traditional offline diagnostic methods, enhancing the real‐time diagnosis of distribution network cable insulation conditions. This study established a 10 kV distribution network cable test platform and prepared typical defective cables subjected to moisture and long‐term thermal aging. Using COMSOL finite element electromagnetic simulation, the magnetic flux evolution laws of the cable insulation under typical defects were obtained. Experimental tests provided the harmonic current characteristics and statistical features of cables with typical defects. Based on these data, a method for analysing the degradation degree of distribution network cables was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis. Furthermore, a defect‐type identification method based on cluster analysis was proposed. Results indicate that the odd harmonics and the 4th harmonic of the distribution network cable's harmonic current are closely related to the cable's degradation state. A model integrating principal component analysis (PCA) data dimensionality reduction and expectation‐maximization clustering analysis achieved a recognition accuracy of up to 75.64% in distinguishing between moisture‐affected and normal cable states. The proposed on‐line detection and evaluation methods can effectively identify high‐risk cables with latent defects. [ABSTRACT FROM AUTHOR]

People living with cognitive impairments face new forms of disablement in the context of transport digitalisation, an issue recently catalysed by controversies regarding rail ticket office closures. Transport can dramatically impact the lives of people diagnosed with dementia, who often find their mobility suddenly and dramatically impaired. Unfortunately, sociological analysis of cognitive disability has traditionally been undermined by under‐theorisation. One solution can be found in classic bioethical work on hypercognitivism—the veneration of cognitive acuity—and its disabling consequences. A hypercognitive approach can nurture an attentiveness to the specificities of digital disablement. Here, disability does not emerge from digitalisation inherently, but is instead intensified by the implementation of digitalisation in line with value commitments. A more robust sociology of cognitive disability could better represent the interests of people with cognitive impairments and resist the new forms of disability that current digitalisation risks spreading. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to explore factors affecting the progression of neovascular age‐related macular degeneration (nAMD) and identify predictive factors that can estimate the duration of intravitreal treatments. Methods: This retrospective real‐world study included 421 nAMD patients treated at the Kuopio University Hospital during years 2007–2021. The collected data included background demographics, treatment history, visual acuity and retinal biomarker analysis. Impact of baseline factors on age at diagnosis, treatment duration, received treatment intensity and visual acuity gains were analysed. Results: Heavy smoking and high body mass index (BMI) were associated with an earlier onset, while the use of anticoagulation and anti‐aggregation medication were associated with a later onset of nAMD. A low number of injections during the first year of treatment and the presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p = 0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRF) and complete RPE and outer retinal atrophy (cRORA; 20.7% vs. 5%, p = 0.02) were observed in patients with IRF. Conclusions: Our results reveal that heavy smoking and high BMI are accelerating factors for earlier emergence of nAMD, while the presence of IRF results in a fast‐progressing disease. More intriguingly, the link between IRF and appearance of subretinal drusenoid deposits, HRF, and increased retinal atrophy was observed. [ABSTRACT FROM AUTHOR]

Heat stress induced damage to the gastrointestinal barrier can induce local and systemic inflammatory reactions implicated in heat-stroke. Gastrointestinal barrier damage has been shown to be greater in older relative to young adults following hyperthermia. However, comparisons between young and older adults have been limited to brief exposures (3 h), which may not reflect the duration of heat stress experienced during heat waves. We therefore evaluated markers of intestinal epithelial damage (log transformed intestinal fatty acid binding protein, IFABPLOG), microbial translocation (soluble cluster of differentiation 14, sCD14LOG), and systemic inflammation (tumour necrosis factor alpha, TNF-αLOG; interleukin 6, IL-6LOG; C-reactive protein, CRP) in 19 young (interquartile range: 21–27 years; 10 females) and 37 older (68–73 years; 10 females) adults before and after 9 h of rest in 40 °C (9% relative humidity). The magnitude of the increase in IFABPLOG was 0.38 log pg/mL (95% CI, 0.10, 0.65 log pg/mL) greater in the older relative to young cohort (P = 0.049) after 9 h heat exposure. At baseline both IL-6LOG and CRP concentrations were higher in the older (IL-6: 2.67 (1.5) log pg/mL, CRP: 0.28 (1.5) mg/mL) relative to the young (IL-6: 1.59 log pg/mL, SD 1.2; CRP: 0.11 mg/mL, SD 1.7) group (both P ≤ 0.001). The change in IL-6 and CRP was similar between groups following 9 h heat exposure (IL-6: P = 0.053; CRP: P = 0.241). Neither sCD14LOG and TNF-αLOG were different between groups at baseline nor altered after 9 h heat exposure. Our data indicate that age may modify intestinal epithelial injury following 9 h of passive heat exposure. [ABSTRACT FROM AUTHOR]

Summary: This review addresses the knowledge gap surrounding ergothioneine which is a naturally occurring antioxidant, by examining both its beneficial properties and the challenges associated with its study. Ergothioneine, often termed a 'longevity vitamin', is present in various foods such as mushrooms, grains and certain animal tissues and is synthesised by specific microorganisms. Despite its recognised potential in promoting healthier and extended lifespans, the mechanisms and full spectrum of its effects remain inadequately understood. This article provides a balanced overview of ergothioneine, covering its prevalence, methods for quantification and a wide range of bioactivities, while its antioxidant capabilities, including the neutralisation of free radicals and reactive oxygen species, highlight its promise for enhancing cellular health and preventing age‐related diseases. In addition to that, this review also discusses the limitations and gaps in current research. Notably, ergothioneine's bioaccumulation in tissues vulnerable to oxidative stress suggests its significant role in longevity. Preliminary studies suggest benefits such as reduced inflammation, protection of mitochondrial function and support for brain health, yet comprehensive studies are required to fully understand its mechanisms. This review aims to present an unbiased and thorough understanding of ergothioneine, emphasising the need for further research to unlock its full potential in human health and ageing. [ABSTRACT FROM AUTHOR]

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l -arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l -arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure. Conclusion It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l -arginine supplementation. [ABSTRACT FROM AUTHOR]

Malnutrition is a prevalent, yet often underdiagnosed and undertreated, condition in older adults. It is characterized by weight loss and/or reduced muscle mass due to diminished caloric intake, inflammation, and/or disease burden. In return, malnutrition can lead to diminished skeletal muscle functionality and disability, among others. Malnutrition plays a crucial role in the pathogenesis of two prevalent geriatric syndromes, namely sarcopenia and frailty. The complex interplay between malnutrition, sarcopenia, and frailty significantly impacts the older population, leading to increased morbidity, mortality, hospitalization rates, quality-of-life, and healthcare costs. Given the prognostic significance of malnutrition in geriatric care, recent guidelines emphasized the role of nutritional support in vulnerable populations. A group of vulnerable populations to malnutrition, sarcopenia, and frailty are older patients with hip fractures, cancer patients, and those with sarcopenic dysphagia. This article highlights the importance of individualized nutritional assessment and treatment in the management of vulnerable populations such as older patients with hip fractures, cancer, and those suffering from sarcopenic dysphagia. It presents practical protocols and guidelines that can be instrumental in enhancing the nutritional care of these groups, thereby improving their overall health outcomes. [ABSTRACT FROM AUTHOR]

The aim of our experiment was to analyse the effect of the emotional valence (positive, negative, or neutral) on true and false recognition, matching the arousal, frequency, concreteness, and associative strength of the study and recognition words. Fifty younger adults and 46 healthy older adults performed three study tasks (with words of different valence: positive, negative, neutral) and their corresponding recognition tests. Two weeks later, they performed the three recognition tests again. The results show that words with a negative valence produced less true recognition and less false recognition than words with a positive or neutral valence, in both younger and older adults, on the immediate recognition test. This pattern of results was also found in the younger adults on the delayed recognition test, whereas in the older participants, these differences disappeared. Thus, when arousal is controlled, both younger and older adults tend to recognise negative information worse than positive or neutral information, but they also commit fewer errors. Results would suggest that the greater arousal commonly associated with negative stimuli, rather than their own valence, could explain some of the contradictory results found in the literature. [ABSTRACT FROM AUTHOR]

Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC). Men with AUD (n = 108, mean age = 52.4, SD = 8.6) were recruited in a detoxification unit, and HC (n = 80, mean age = 50.04, SD = 9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR. Telomere length did not differ between individuals with AUD and HC (p = 0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p = 0.018) or without comorbidity (p = 0.018). Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age. • Telomere length is a marker of ageing. • Telomere length did not differ between individuals with AUD and controls. • Individuals with externalizing disorders have longer telomere length. [ABSTRACT FROM AUTHOR]

Context: The proportion of the elderly population is on the rise across the globe, and with it the prevalence of age-related neurodegenerative diseases. The gut microbiota, whose composition is highly regulated by dietary intake, has emerged as an exciting research field in neurology due to its pivotal role in modulating brain functions via the gut-brain axis. Objectives: We aimed at conducting a systematic review of preclinical and clinical studies investigating the effects of dietary interventions on cognitive ageing in conjunction with changes in gut microbiota composition and functionality. Methods: PubMed and Scopus were searched using terms related to ageing, cognition, gut microbiota and dietary interventions. Studies were screened, selected based on previously determined inclusion and exclusion criteria, and evaluated for methodological quality using recommended risk of bias assessment tools. Results: A total of 32 studies (18 preclinical and 14 clinical) were selected for inclusion. We found that most of the animal studies showed significant positive intervention effects on cognitive behavior, while outcomes on cognition, microbiome features, and health parameters in humans were less pronounced. The effectiveness of dietary interventions depended markedly on the age, gender, degree of cognitive decline and baseline microbiome composition of participants. Conclusion: To harness the full potential of microbiome-inspired nutrition for cognitive health, one of the main challenges remains to better understand the interplay between host, his microbiome, dietary exposures, whilst also taking into account environmental influences. Future research should aim toward making use of host-specific microbiome data to guide the development of personalized therapies. [ABSTRACT FROM AUTHOR]

Background: Existing research shows that older people with severe mental health problems need different forms of support in daily life and in the community to lead an active and meaningful life. A common form of support for people with severe mental health problems in Sweden is attendance at community‐based day centres (DCs). However, knowledge of staff and managers' experiences of how people ageing with severe mental health problems are supported in DCs is scarce. Aim: The aim was to explore DC staff and managers' experiences of how people ageing with severe mental health problems are supported in DCs during the retirement process. Method/Procedure: Telephone interviews were conducted with managers in 27 municipalities in southern Sweden. In addition, focus groups were held with personnel from a total of nine different DCs. The material was analysed using content analysis. Results: The results showed that older people who receive support in community‐based mental health care were viewed as a neglected group with complex needs, and the informants (managers and staff) had few policies to guide them when providing support. This made the informants desire more knowledge about best practices to support the target group. One theme emerged, Minding the gap between ideal and reality while working with a neglected group with complex needs, with three categories: Reasoning around unmet needs, Navigating in a muddled organisation, and Wishing for an enriched service. Conclusion/Practical Application: Together with previous research, the results can contribute to increase awareness about an overlooked group at risk of being neglected and the pitfalls that impact the possibility to guide this target group in their recovery journey. Further research focusing on the target group's own experience of their everyday life situations is also needed. [ABSTRACT FROM AUTHOR]

This study examines the perspectives and experiences of older lifelong participants in outdoor education/recreation. 32 participants, women (11) and men (21), aged 60-84 provided narratives of their lifelong engagements in the outdoors in nature-based activities. They were invited to write freely on their early experiences and their current engagements in the outdoors. The purpose was to explore and understand why and how serious lifelong older participants continued with their outdoor activities. This paper considers participants' current embodied engagements. The evidence suggests that as they age, their bodies become less able to deal with discomfort. Yet, the participants, as a consequence of their lifelong knowledge and experience, manage injuries and ill-health, choosing to adapt in various ways to enable their continued engagement/enjoyment in being active in nature. The study stresses the significance of lifelong engagement in the outdoors and the necessity for opportunities for outdoor nature -based experiences throughout the lifespan. [ABSTRACT FROM AUTHOR]

The communication between dorsal premotor cortex (PMd) and primary motor cortex (M1) is important for visuomotor adaptation, but it is unclear how this relationship changes with advancing age. The present study recruited 21 young and 23 older participants for two experimental sessions during which intermittent theta burst stimulation (iTBS) or sham was applied over PMd. We assessed the effects of PMd iTBS on M1 excitability using motor evoked potentials (MEP) recorded from right first dorsal interosseous when single-pulse transcranial magnetic stimulation (TMS) was applied with posterior-anterior (PA) or anterior-posterior (AP) currents; and adaptation by quantifying error recorded during a visuomotor adaptation task (VAT). PMd iTBS potentiated PA (P < 0.0001) and AP (P < 0.0001) MEP amplitude in both young and older adults. PMd iTBS increased error in young adults during adaptation (P = 0.026), but had no effect in older adults (P = 0.388). Although PMd iTBS potentiated M1 excitability in both young and older adults, the intervention attenuated visuomotor adaptation specifically in young adults. • The functional role of dorsal premotor cortex (PMd) is altered with advancing age. • PMd theta burst stimulation (TBS) attenuates visuomotor adaptation in young adults. • PMd TBS does not modulate visuomotor adaptation in older adults. [ABSTRACT FROM AUTHOR]

Background and Purpose: The mechanistic target of rapamycin (mTOR) signalling pathway is a key regulator of cell growth and metabolism. Its deregulation is implicated in several diseases. The macrolide rapamycin, a specific inhibitor of mTOR, has immunosuppressive, anti‐inflammatory and antiproliferative properties. Recently, we identified tacrolimus, another macrolide immunosuppressant, as a novel activator of TRPM8 ion channels, involved in cold temperature sensing, thermoregulation, tearing and cold pain. We hypothesized that rapamycin may also have agonist activity on TRPM8 channels. Experimental Approach: Using calcium imaging and electrophysiology in transfected HEK293 cells and wildtype or Trpm8 KO mouse DRG neurons, we characterized rapamycin's effects on TRPM8 channels. We also examined the effects of rapamycin on tearing in mice. Key Results: Micromolar concentrations of rapamycin activated rat and mouse TRPM8 channels directly and potentiated cold‐evoked responses, effects also observed in human TRPM8 channels. In cultured mouse DRG neurons, rapamycin increased intracellular calcium levels almost exclusively in cold‐sensitive neurons. Responses were markedly decreased in Trpm8 KO mice or by TRPM8 channel antagonists. Cutaneous cold thermoreceptor endings were also activated by rapamycin. Topical application of rapamycin to the eye surface evokes tearing in mice by a TRPM8‐dependent mechanism. Conclusion and Implications: These results identify TRPM8 cationic channels in sensory neurons as novel molecular targets of the immunosuppressant rapamycin. These findings may help explain some of its therapeutic effects after topical application to the skin and the eye surface. Moreover, rapamycin could be used as an experimental tool in the clinic to explore cold thermoreceptors. [ABSTRACT FROM AUTHOR]

The film ' Age is Just a Bingo Number ' is a mid-length (40 minutes) participatory documentary exploring the experiences of a community of ageing Italians in Newcastle upon Tyne, UK. As a product of social science research, this documentary aims to bridge the gap between academia and the general audience, by disseminating research findings in creative ways, through art practices. This documentary constitutes an empirical contribution to the sociology of community studies, by exploring the social interactions of a small place-based group of older migrants. Hence, the documentary introduces the audience to a recreational centre in the heart of the city, where the participants gather on a weekly basis to play Bingo. This place, and the sense of community it conveys, aims at promoting social aspects of the environment for older people. Furthermore, by illustrating how older migrants can become closely attached to places, it aims at raising awareness of issues of ageing in the context of migration. In this sense, the film is an original contribution to the sociology of ageing and transnational migration. [ABSTRACT FROM AUTHOR]

Copyright of Ethik in der Medizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke's Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [β (95% CI) − 1.354 (− 2.655, − 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [β (95% CI) − 5617.182 (− 11062.762, − 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function. [ABSTRACT FROM AUTHOR]

Characterizing cortical plasticity becomes increasingly important for identifying compensatory mechanisms and structural reserve in the ageing population. While cortical thickness (CT) largely contributed to systems neuroscience, it incompletely informs about the underlying neuroplastic pathophysiology. In turn, microstructural characteristics may correspond to atrophy mechanisms in a more sensitive way. Fractional anisotropy, a diffusion tensor imaging (DTI) measure, is inversely related to cortical histologic complexity. Axial diffusivity and radial diffusivity are assumed to be linked to the density of structures oriented perpendicular and parallel to the cortical surface, respectively. We hypothesized (1) that cortical DTI will reveal microstructural correlates for hemispheric specialization, particularly in the language and motor systems, and (2) that lateralization of cortical DTI parameters will show an age effect, paralleling age‐related changes in activation, especially in the prefrontal cortex. We analysed data from healthy younger and older adult participants (N = 91). DTI and CT data were extracted from regions of the Destrieux atlas. Diffusion measures showed lateralization in specialized motor, language, visual, auditory and inferior parietal cortices. Age‐dependent increased lateralization for DTI measures was observed in the prefrontal, angular, superior temporal and lateral occipital cortex. CT did not show any age‐dependent alterations in lateralization. Our observations argue that cortical DTI can capture microstructural properties associated with functional specialization, resembling findings from histology. Age effects on diffusion measures in the integrative prefrontal and parietal areas may shed novel light on the atrophy‐related plasticity in healthy ageing. [ABSTRACT FROM AUTHOR]

Background: Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses. Methods: A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline. Results: Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction. Conclusions: Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation. Trial registration: 28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981. [ABSTRACT FROM AUTHOR]

Background: Mouse brains can contain specific polyglucosan aggregates known as Periodic Acid-Schiff (PAS)-granules. Generated in astrocytes, these granules increase with age and exhibit neo-epitopes of carbohydrate nature that are recognized by natural IgM antibodies (IgMs). The existence of neoepitopes on PAS granules suggests the presence of neoepitopes in other brain structures, and this is investigated here. To this end, brain sections from SAMP8 and ICR-CD1 mice were examined at different ages. Results: We have identified two novel structures that, apart from PAS granules, are recognized by natural IgMs. On one side, IgM reactive (IgM+) granular structures which are placed in the longitudinal fissure, the quadrigeminal cistern, and a region that extends from the quadrigeminal cistern to the interpeduncular cistern. This last region, located between the telencephalon and both the mesencephalon and diencephalon, is designated henceforth as the fissura magna, as it is indeed a fissure and the largest in the brain. As all these regions are extraparenchymal (EP), the IgM+ granules found in these zones have been named EP granules. These EP granules are mainly associated with fibroblasts and are not stained with PAS. On the other side, some IgM+ astrocytes have been found in the glia limitans, near the above-mentioned fissures. Remarkably, EP granules are more prevalent at younger ages, while the number of IgM+ astrocytes increases with age, similarly to the already described evolution of PAS granules. Conclusions: The present work reports the presence of two brain-related structures that, apart from PAS granules, contain neo-epitopes of carbohydrate nature, namely EP granules and IgM+ astrocytes. We suggest that EP granules, associated to fibroblasts, may be part of a physiological function in brain clearance or brain-CSF immune surveillance, while both PAS granules and IgM+ astrocytes may be related to the increasing accumulation of harmful materials that occurs with age and linked to brain protective mechanisms. Moreover, the specific localisation of these EP granules and IgM+ astrocytes suggest the importance of the fissura magna in these brain-related cleaning and immune functions. The overall results reinforce the possible link between the fissura magna and the functioning of the glymphatic system. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is commonly managed in general practice, with established guidelines for diagnosis and management. CKD is more prevalent in the older population, and is associated with lifestyle diseases as well as social deprivation. Older patients also commonly experience multimorbidity. Current CKD guidelines do not take age into account, with the same diagnostic and management recommendations for patients regardless of their age. We sought to investigate general practitioners' (GPs') approach to older patients with CKD, and whether their assessment and management differed from guideline recommendations. We explored the reasons for variation from guideline recommendations. Methods: This was a mixed methods study of Australian GPs. An online anonymous survey about the use of CKD guidelines, and assessment and management of CKD was sent to 9500 GPs. Four hundred and sixty-nine (5%) of GPs responded, and the survey was completed by 399 GPs. Subsequently, 27 GPs were interviewed in detail about their diagnostic and management approach to older patients with declining kidney function. Results: In the survey, 48% of GPs who responded found the CKD guidelines useful for diagnosis and management. Four themes arose from our interviews: age-related decline in kidney function; whole person care; patient-centred care; and process of care that highlighted the importance of continuity of care. GPs recognised that older patients have an inherently high risk of lower kidney function. The GPs reported management of that higher risk focused on managing the whole person (not just a single disease focus) and being patient-centred. Patient-centred care expressed the importance of quality of life, shared decision making and being symptom focused. There was also a recognition that there is a difference between a sudden decline in kidney function and a stable but low kidney function and GPs would manage these situations differently. Conclusions: GPs apply guidelines in the management of CKD in older patients using a patient-centred and whole person approach to care. Older patients have a high prevalence of multimorbidity, which GPs carefully considered when applying existing CKD-specific guidelines. Future iterations of CKD Guidelines need to give due consideration to multimorbidity in older patients that can adversely impact on kidney function in addition to the expected age-related functional decline. [ABSTRACT FROM AUTHOR]

Introduction Objectives Materials and methods Results Discussion and conclusion Several robust epidemiological studies suggest that men are often engaged in sexual relationships with younger women with a variable, age‐dependent age difference. However, the ageing process determines a significant worsening of the andrological status, which favors the onset of erectile dysfunction and hypogonadism.To analyze the effects of differences in age between the partners [delta (Δ) age (M − F)] on patients referring to the Andrology Unit of Careggi University Hospital for male sexual dysfunction.A monocentre cohort of 4055 male subjects was evaluated by SIEDY structured interview. The cross‐sectional analysis assessed the psychobiological and relational correlates. The rate of forthcoming major cardiovascular events (MACE) was investigated in the longitudinal analysis. All the models have been adjusted for age, education, lifestyle, and chronic disease score.∆ age (M–F) shows a stepwise increase, according to the increasing age bands of the male partner. ∆ age (M–F) was associated with a greater number of children, at the cost of more conflictual relationships within the family. The phenotype of these relationships is characterized by the report of a partner with a higher sexual desire and a higher ability to reach climax. Men seeking a younger partner show more often a histrionic personality (p = 0.023) and higher testosterone levels (p = 0.032). However, having a younger partner doesn't improve the ability to obtain a full erection. Kaplan–Maier analysis of a longitudinal subgroup of patients followed longitudinally (N = 1402) for 4.3 ± 2,59 years, showed that patients in the fourth quartile had a higher rate of forthcoming MACE versus those in the first quartile (p = 0.005).In subjects with sexual dysfunctions (as in the general population) age‐different relationships increase as a function of male ageing. A greater Δ age (M–F) is associated with specific men and relationship features and a higher risk of MACE. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodResultsConclusionPopulation ageing raises major public health and psychosocial challenges. Particularly, lesbian, gay, and bisexual (LGB) older people may face increased vulnerabilities and marginalization when compared to their non-LGB (heterosexual) counterparts, which may entail more risks for their mental health. The aim of this study was to comparatively evaluate the levels of protective – social support, spirituality, and resilience and stress factors – loneliness and ageism – among LGB and non-LGB older adults, and their impact on psychological distress (PD).A sample of 647 people aged 60 years or older (M = 66.01; SD = 4.93) was collected, 368 non-LGB and 279 LGB. Participation was carried out through an online survey in Portugal.LGB older adults had lower scores on all protective factors, except on social support from friends, and higher levels on all stress factors, except on hostile ageism, compared to non-LGB older adults. Further, resilience and loneliness were the main predictors of PD regardless of the sexual orientation. Stress factors explained the levels of PD over and above the effects of protective factors, both among LGB and non-LGB older adults.Psychological distress in aging presents different protective and stressful factors according to the sexual orientation of older adults. More comparative studies are suggested in the intersection between ageing and sexual orientation. [ABSTRACT FROM AUTHOR]

Liner materials have extensive applications in automobile industry, packaging, and aeronautics. One of the specific uses of such materials is in thermal barrier, coating rockets, missile, and other systems used in space and defense. Each liner material exhibits different properties according to their chemical structure and composition. In this study, accelerated thermal aging of the liner material, silicone‐hollow glass microsphere composite (SHGC) has been studied along with the determination of its life span. The effect of such aging on the thermal properties of SHGC has been studied using thermogravimetry. Activation energy of the process has been determined to be in the range of 45–55 KJmol−1. The results have been compared with already reported silicon polymers. Shelf‐life of SHGC composite has also been determined using Arrhenius model. Stochastic model has been applied to determine the lower and upper limits of shelf‐life. Shelf‐life of SHGC is found to be 24 years with 28 and 18 years of upper and lower error limits. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age‐associated hyperphosphatemia in these changes.We used C57BL6 mice to study an ageing model in vivo and human lung fibroblasts were treated with a phosphate donor, beta‐glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET‐1 system by western blot or RT‐PCR.Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro‐inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NFkB to the MCP‐1 or FN promoters. BGP increased ECE‐1 expression by inducing NFkB binding to the ECE‐1 promoter. QNZ, an NFkB inhibitor, blocked these effects. When ECE‐1 was inhibited with phosphoramidon, BGP‐induced inflammation and fibrosis were significantly reduced, suggesting a role for ET‐1 in BGP‐mediated effects.ET‐1 produced effects similar to those of BGP, which were also dependent on NFkB. To study the pathophysiological relevance of hyperphosphatemia in vivo, a low‐P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet.These results suggest that age‐related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET‐1 and NFkB activation. [ABSTRACT FROM AUTHOR]

Cellular senescence is a response to many stressful insults. DNA damage is a consistent feature of senescent cells, but in many cases its source remains unknown. Here, we identify the cellular endonuclease caspase-activated DNase (CAD) as a critical factor in the initiation of senescence. During apoptosis, CAD is activated by caspases and cleaves the genomic DNA of the dying cell. The CAD DNase is also activated by sub-lethal signals in the apoptotic pathway, causing DNA damage in the absence of cell death. We show that sub-lethal signals in the mitochondrial apoptotic pathway induce CAD-dependent senescence. Inducers of cellular senescence, such as oncogenic RAS, type-I interferon, and doxorubicin treatment, also depend on CAD presence for senescence induction. By directly activating CAD experimentally, we demonstrate that its activity is sufficient to induce senescence in human cells. We further investigate the contribution of CAD to senescence in vivo and find substantially reduced signs of senescence in organs of ageing CAD-deficient mice. Our results show that CAD-induced DNA damage in response to various stimuli is an essential contributor to cellular senescence. Synopsis: Senescent cells are characterized by DNA damage, but the underlying mechanisms in many contexts remain little understood. Our study identifies and characterizes an important contribution of the caspase-activated DNase (CAD) to senescence-associated DNA damage in vitro and in mice. CAD is required for a normal cellular senescence response to various stimuli. CAD activation is sufficient for the induction of senescence in vitro. CAD-dependent activation of cGAS induces production of components of the senescence-associated secretory phenotype. While strong apoptotic stimuli kill the cell, weaker stimuli can cause caspase activation at sub-lethal levels, leading to CAD activation and senescence. Sub-lethal apoptotic signals activate the caspase-activated DNase (CAD), leading to genomic DNA cleavage and the induction of senescence. [ABSTRACT FROM AUTHOR]

Objective: Frailty and hypoproteinaemia are common in older individuals. Although there is evidence of a correlation between frailty and hypoproteinaemia, the relationship between frailty and hypoproteinaemia in hospitalized/critically ill and older community residents has not been clarified. Therefore, the aim of our meta-analysis was to evaluate the associations between frailty and hypoproteinaemia in different types of patients. Methods: A systematic retrieval of articles published in the PubMed, Embase, Medline, Web of Science, Cochrane, Wanfang, and CNKI databases from their establishment to April 2024 was performed to search for studies on the associations between severity of frailty or prefrailty and hypoproteinaemia in older adults. The Newcastle‒Ottawa Scale and the Agency for Healthcare Research and Quality Scale were used to assess study quality. Results: Twenty-two studies were included including 90,351 frail older people were included. Meta-analysis revealed an association between frailty or prefrailty and hypoproteinaemia (OR = 2.37, 95% CI: 1.47, 3.83; OR = 1.62, 95% CI: 1.23, 2.15), there was no significant difference in the risk of hypoproteinaemia between patients with severe frailty and those with low or moderate frailty (OR = 0.62, 95% CI:0.44, 0.87). The effect of frailty on the occurrence of hypoproteinaemia was more obvious in hospitalized patients/critically ill patients than in surgical patients (OR = 3.75, 95% CI: 2.36, 5.96), followed by older community residents (OR = 2.30, 95% CI: 1.18, 4.49). Conclusion: Frailty is associated with hypoproteinaemia in surgical patients, hospitalized older patients and older community residents. Future studies should focus on the benefits of albumin supplementation in preventing or alleviating frailty and related outcomes in the future. [ABSTRACT FROM AUTHOR]

The study's objective is to create a method to select the best course of maintenance action for each state of ship propulsion system degradation while considering both the present and future costs and associated carbon intensity indicator, CII, rates. The method considers the effects of wind and wave action when considering fouling and ageing. The ship resistance in calm, wave, and wind conditions has been defined using standard operating models, which have also been used to estimate the required engine power, service speed, fuel consumption, generated CO2, CII, and subsequent maintenance costs. The maintenance takes into consideration the effects of profit loss because of lost opportunities and efficiency over time. Any maintenance choice has total costs associated with it, including extra fuel, upkeep, and missed opportunities. Using a discrete-time Markov chain, the ship's propulsion system maintenance schedule is optimized. A decision has been reached regarding the specific maintenance measures to be undertaken for each state of the Markov chain among various alternatives. The choice of optimal maintenance is related to a Markov decision process and is made by considering both the current and future costs. The developed method can forecast the propulsion system's future states and any required maintenance activities. [ABSTRACT FROM AUTHOR]

Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55–80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 normal aged eyes (age 57–88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included. Semithin sections and fellow-eye paraffin sections were additionally examined. BLinD was defined as a diffuse layer of electron-lucent vesicles external to the retinal pigment epithelium (RPE) basement membrane by TEM and was graded as follows: (i) Grade 0, absence of a continuous layer; (ii) Grade 1, a continuous layer up to three times the thickness of the RPE basement membrane (0.9 µm); (iii) Grade 2, a continuous layer greater than 0.9 µm. Bruch's membrane (BrM) hyalinisation and RPE abnormalities were determined by light microscopic examination of corresponding semithin and paraffin sections. Results: BLinD was identified in both normal (30%) and normal aged (62.5%) eyes. BLinD was thicker in normal aged eyes (p = 0.045; 95% CI 0.04–3.4). BLinD thickness positively correlated with both the degree of BrM hyalinisation (p = 0.049; 95% CI 0.05–2.69) and increasing microscopic RPE abnormalities (p = 0.022; 95% CI 0.188–2.422). RPE abnormalities were more likely to be observed in eyes with increased BrM hyalinisation (p = 0.044; 95% CI 0.61–4.319). Conclusions: BLinD is most likely an age-related deposit rather than a specific lesion of AMD. Its accumulation is associated with increasing BrM hyalinisation and microscopic RPE abnormalities, suggesting a relationship with dysregulated RPE metabolism and/or transport. [ABSTRACT FROM AUTHOR]

In humans, gut microbiome (GM) differences are often correlated with, and sometimes causally implicated in, ageing. However, it is unclear how these findings translate in wild animal populations. Studies that investigate how GM dynamics change within individuals, and with declines in physiological condition, are needed to fully understand links between chronological age, senescence and the GM, but have rarely been done. Here, we use longitudinal data collected from a closed population of Seychelles warblers (Acrocephalus sechellensis) to investigate how bacterial GM alpha diversity, composition and stability are associated with host senescence. We hypothesised that GM diversity and composition will differ, and become more variable, in older adults, particularly in the terminal year prior to death, as the GM becomes increasingly dysregulated due to senescence. However, GM alpha diversity and composition remained largely invariable with respect to adult age and did not differ in an individual's terminal year. Furthermore, there was no evidence that the GM became more heterogenous in senescent age groups (individuals older than 6 years), or in the terminal year. Instead, environmental variables such as season, territory quality and time of day, were the strongest predictors of GM variation in adult Seychelles warblers. These results contrast with studies on humans, captive animal populations and some (but not all) studies on non‐human primates, suggesting that GM deterioration may not be a universal hallmark of senescence in wild animal species. Further work is needed to disentangle the factors driving variation in GM‐senescence relationships across different host taxa. [ABSTRACT FROM AUTHOR]

The hair bundle of cochlear hair cells comprises specialized microvilli, the stereocilia, which fulfil the role of mechanotransduction. Genetic defects and environmental noise challenge the maintenance of hair bundle structure, critically contributing to age‐related hearing loss. Stereocilia fusion is a major component of the hair bundle pathology in mature hair cells, but its role in hearing loss and its molecular basis are poorly understood. Here, we utilized super‐resolution expansion microscopy to examine the molecular anatomy of outer hair cell stereocilia fusion in mouse models of age‐related hearing loss, heightened endoplasmic reticulum stress and prolonged noise exposure. Prominent stereocilia fusion in our model of heightened endoplasmic reticulum stress, Manf (Mesencephalic astrocyte‐derived neurotrophic factor)‐inactivated mice in a background with Cadherin 23 missense mutation, impaired mechanotransduction and calcium balance in stereocilia. This was indicated by reduced FM1‐43 dye uptake through the mechanotransduction channels, reduced neuroplastin/PMCA2 expression and increased expression of the calcium buffer oncomodulin inside stereocilia. Sparse BAIAP2L2 and myosin 7a expression was retained in the fused stereocilia but mislocalized away from their functional sites at the tips. These hair bundle abnormalities preceded cell soma degeneration, suggesting a sequela from stereociliary molecular perturbations to cell death signalling. In the age‐related hearing loss and noise‐exposure models, stereocilia fusion was more restricted within the bundles, yet both models exhibited oncomodulin upregulation at the fusion sites, implying perturbed calcium homeostasis. We conclude that stereocilia fusion is linked with the failure to maintain cellular proteostasis and with disturbances in stereociliary calcium balance. Key points: Stereocilia fusion is a hair cell pathology causing hearing loss.Inactivation of Manf, a component of the endoplasmic reticulum proteostasis machinery, has a cell‐intrinsic mode of action in triggering outer hair cell stereocilia fusion and the death of these cells.The genetic background with Cadherin 23 missense mutation contributes to the high susceptibility of outer hair cells to stereocilia fusion, evidenced in Manf‐inactivated mice and in the mouse models of early‐onset hearing loss and noise exposure.Endoplasmic reticulum stress feeds to outer hair cell stereocilia bundle pathology and impairs the molecular anatomy of calcium regulation.The maintenance of the outer hair cell stereocilia bundle cohesion is challenged by intrinsic and extrinsic stressors, and understanding the underlying mechanisms will probably benefit the development of interventions to promote hearing health. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions To investigate: (i) whether mood states associated with bipolar disorder are associated with poorer quality of life in older adults, and (ii) what are some of the predictors of quality of life in older adults with mood states associated with bipolar disorder.The authors completed a cross‐sectional multilevel analysis of panel data from seven waves of The English Longitudinal Study of Ageing dataset. The main analysis included 567 participants who reported experiencing mood states associated with bipolar disorder. Some participants reported this in more than one wave, resulting in 835 observations of mood states associated with bipolar disorder across the seven waves. Quality of life was assessed using the Control, Autonomy, Self‐realization, and Pleasure‐19 (CASP‐19) measure.The presence of mood states associated with bipolar disorder was significantly associated with poorer quality of life, even after controlling for multiple covariates (age, sex, social isolation, loneliness, alcohol use, education level, and economic status). Loneliness significantly predicted poorer quality of life in older adults with mood states associated with bipolar disorder. In contrast, higher educational attainment and being female predicted better quality of life in this group.Older adults with mood states associated with bipolar disorder have potentially worse quality of life compared to the general population, which may be partly driven by loneliness. This has ramifications for the support offered to this population and suggests that treatments should focus on reducing loneliness to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion This study was designed to compare the effects of mental load, caused by concurrent auditory tasks, on attended and non‐attended visual stimuli in older and younger adults.Participants performed a visual orientation discrimination task involving two spatially separated Gabor patches of 4 cycles/degree and 55% contrast. Participants received either a valid‐cue, invalid‐cue or a neutral‐cue for the patch whose orientation they were required to determine. An auditory n‐back task was performed simultaneously to impose mental load. Repeated‐measures ANOVA was used for investigation of main effects and interactions of ageing, mental load and attention condition on orientation discrimination.A total of 27 younger (mean age ± SD, 22.6 ± 1.3 years) and 23 older adults (54.7 ± 4.3 years) participated in the study. There was a significant effect of age (p = 0.01) and mental load (p < 0.001) on the proportion of correct orientation discrimination responses. Attentional condition significantly affected the proportion of correct responses (p = 0.02), but there was no significant interaction between attention, mental load and age group (p = 0.85). There was no overall difference in the proportion of no responses (the proportion of trials in which the participants failed to respond) between the two age groups (p = 0.53) nor on the overall effect of attention on the proportion of no responses (p = 0.25). There was, however, a significant effect of mental load on the proportion of no responses (p = 0.002).Although mental load reduced performance equally for both age groups and for all attentional conditions, older adults had poorer overall performance. Therefore, a given mental load is more likely to drive older observers to unacceptable levels of task performance. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions First‐line managers in Swedish communities have responsibility for that care to older people is provided, staffing is sufficient and the budget is balanced in their unit. It is a struggle with limited resources due to a growing population in need of care. This can lead to missed nursing care. The aim was to describe first‐line managers´ perceptions of missed nursing care in community health care for older people.A qualitative design with a phenomenographic approach, interviewing 24 first‐line managers. Ethics approval for the study was received from the Research Ethics Committee at Karlstad University (Dnr HNT 2020/566).The results are shown in six descriptive categories containing 15 perceptions. The descriptive categories are ‘occurrence of missed nursing care’, ‘becoming aware of missed nursing care’, ‘reasons for missed nursing care’, ‘missed nursing care has consequences for the older persons’, ‘missed nursing care has consequences for the staff’ and ‘taking action to decrease missed nursing care’.It is important for first‐line managers to become aware of the existence and reasons for missed nursing, as it has consequences for older people and staff. Managers need to take missed nursing care seriously in order to work with improvements for maintaining good quality of care and patient safety. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the effect of frailty on loneliness among older adults receiving home care, in correlation to their socioeconomic and homebound statuses. This cross-sectional study recruited 218 individuals aged ≥65 years receiving home-based health services from the "Help at Home" program in the Region of Evrytania, Greece through an open invitation from the municipality authorities from March to June 2022. The Tilburg Frailty Indicator (TFI) was used for the evaluation of frailty, the UCLA Loneliness Scale version 3 was used for loneliness, and social isolation was accessed through five questions (living alone, frequency of interaction with children, relatives, friends, and participation in social organizations). The mean age of the participants was 81.48 ± 9.06, 61.9% were female, 54.1% experienced high levels of loneliness (UCLA-3 mean 45.76 ± 11.10 [range 20–68]), and 46.3% of the participants were found to be socially isolated. Also, 58.3% of the individuals were identified as frail (TFI mean 5.95 ± 3.07) [TFI range 0–13], with 57.3% experiencing physical frailty, 43.6% experiencing psychological frailty, and 27.1% experiencing social frailty. An analysis of covariance (ANCOVA) using UCLA-3 as the dependent variable revealed that loneliness across all domains of TFI was significantly higher in participants with frailty (total frailty [Yes] 49.27 vs. [No] 40,87 p < 0.001) (physical frailty [Yes] = 48.99 vs. [No] = 41.42, p < 0.001, psychological: 48.60 vs. 43.57 p < 0.001, and social: 53.38 vs. 42.94 p < 0.001), particularly compared to non-frail individuals, even after adjusting for potential confounding effects (covariates: gender, age, marital status, family status, living status, educational level, annual income, chronic diseases, homebound status, and social isolation). Our findings indicate that frail older adults experienced higher levels of loneliness, suggesting that frailty and loneliness are independently associated among older adults who receive home-based healthcare. [ABSTRACT FROM AUTHOR]

Research suggests that sedentary behavior (SB) and obesity are associated with disabilities in basic activities (BADL) and instrumental (IADL) activities of daily living. However, there is a lack of studies investigating this association in community-dwelling older adults. Thus, the aim of this study was to investigate the association between different SB typologies, isolated and in conjunction with obesity, and their associations with BADL and IADL disabilities in community-dwelling Brazilian older adults. This was a cross-sectional study using data from older adults (≥60 years) who participated in the Brazilian National Health Survey (2019). The exposures were obesity (BMI > 27 kg/m2) and the amount of time spent daily on SB watching television (SB TV < 3 and ≥3 h/day) and engaging in leisure activities (SB leisure < 3 and ≥3 h/day), analyzed both separately and jointly. The outcomes were BADL and IADL disabilities. The main results showed that isolated SB TV ≥ 3 h/day (OR: 1.26; 95% CI: 1.14; 1.39) and SB TV ≥ 3 h/day combined with obesity (OR: 1.55; 95% CI: 1.37; 1.75) increased the odds of BADL and IADL disabilities. Obesity alone (OR: 1.21; 95% CI: 1.07; 1.36) increased only the odds of BADL disabilities. Moreover, SB leisure ≥ 3 h/day without obesity reduced the odds of IADL disabilities (OR: 0.56; 95% CI: 0.41; 0.76). Ideally, older adults should be encouraged to prevent obesity, reduce excessive periods spent in SB watching TV, and increase the daily periods spent in leisure activities, thus minimizing the likelihood of disabilities in functional activities. [ABSTRACT FROM AUTHOR]

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight‐bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing‐related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults. [ABSTRACT FROM AUTHOR]