Virgin coconut oil mitigates ageing-associated oxidative stress and dyslipidaemia in male Wistar rats.

BACKGROUND AND AIM: Ageing often leads to the deterioration of physiological functions, including a decline in antioxidant defences, which can result in various health complications. Exogenous antioxidants have been recognised for their potential to alleviate these age-related health complications. Virgin coconut oil (VCO), known for its antioxidant, anti-inflammatory and anti-lipidemic efficacies, has gained recognition as a functional food with promising benefits. However, the safety of VCO consumption among individuals of the aged and diseased population remains to be fully established. METHODS AND RESULTS: Five experimental groups were established, consisting of one control group and four groups administered either "2 mL" or "4 mL" per kg body weight of "HP-VCO" or "F-VCO" daily for six weeks. Body weight, water, and feed intake were monitored. After six weeks, animals were euthanized, blood and organs were collected for analysis. Oxidative stress and dyslipidemia markers were analysed, and liver tissues underwent histological examination. HP-VCO-administered animals exhibited increased serum total cholesterol and triglycerides, whereas F-VCO-fed animals showed reduced triglyceride levels. LDL-cholesterol levels decreased in all VCO-fed groups, accompanied by increased HDL-cholesterol levels. Additionally, all treated groups showed a slight increase in the HMG Co. A/mevalonate ratio. Both VCO-fed animals displayed elevated reduced glutathione levels and reduced glutathione - S transferase activity. Consistent with these findings, decreased conjugated dienes and thiobarbituric acid reactive substances confirmed the improved redox status. CONCLUSION: The study indicated that F-VCO is advantageous over VCO prepared by hot pressing as it offers protection against oxidative stress and related degenerative diseases.

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

OBJECTIVES: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. METHODS: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. RESULTS: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. CONCLUSIONS: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

The temporal sequence and reciprocal relationships of frailty, social isolation and loneliness in older adults across 21 years.

BACKGROUND: It is unclear whether social isolation and loneliness may precede frailty status or whether frailty may precipitate social isolation and loneliness. We investigated the reciprocal and temporal sequence of social isolation, loneliness, and frailty among older adults across 21 years. METHODS: We used seven waves of the Longitudinal Aging Study Amsterdam from 2302 Dutch older adults (M = 72.6 years, SD = 8.6, 52.1% female) ages 55 or older. Using random intercept cross-lagged panel models, we investigated between- and within-person associations of social isolation and loneliness with frailty. Frailty was measured using the Frailty Index. Loneliness was measured using the 11-item De Jong Gierveld Loneliness Scale. Social isolation was measured using a multi-domain 6-item scale. RESULTS: Social isolation and loneliness were weakly correlated across waves. At the between-person level, individuals with higher levels of frailty tended to have higher levels of social isolation but not loneliness. At the within-person level, the cross-lagged paths indicated that earlier frailty status predicted future social isolation and loneliness over time. However, prior social isolation was not associated with subsequent frailty except at time point 5 (T5). Loneliness at specific time points (T1, T4 and T6) predicted greater frailty at later time points (T2, T5 and T7). The results also supported reciprocal and contemporaneous relations between social isolation, loneliness and frailty. CONCLUSIONS: Social isolation and loneliness are potential outcomes of frailty. Public health policies and health practitioners should prioritise interventions targeting social connection among older adults with pre-frailty or frailty.

Disentangling Anemia in Frailty: Exploring the role of Inflammation.

BACKGROUND: In older patients, frailty and anemia frequently coexist. However, only few studies have been conducted in older patients with multimorbidity and several overlapping causes of anemia, such as inflammation, inadequate nutrition or certain pathologies. This analysis aims to decipher potential factors associated with anemia in older hospital patients with frailty. METHODS: Patients (n=208, age: 62-98 years) were categorized as pre-frail (n=68) and frail (n=140) using the Fried frailty phenotype. We quantified serum concentrations of markers of iron-metabolism (iron, ferritin, transferrin, soluble transferrin receptor, hepcidin), inflammation (interleukin (IL) 6, IL-10 C-reactive protein) and haematology (hemoglobin). Principal component analysis was conducted to evaluate biomarker patterns and associations with frailty were assessed with logistic regression analysis. RESULTS: Anemia prevalence was higher in patients with frailty (84.3% versus 70.6%, p=0.021). Three principal components (PC1-3) were identified. PC1 was characterized by high factor loadings representing inflammation and factor scores differed between patients with pre-frailty and frailty [-0.04 (IQR:1.45) versus -0.51 (IQR:0.87), p<0.001]. PC2 represents macrocytic anemia and thus vitamin B12 or folate deficiency, whereas PC3 indicates hematological pathologies. Only PC1 was associated with frailty status when controlled for age, sex, number of drugs and comorbidities (OR: 2.018, 95%CI: 1.316; 3.094, p=0.001). PC2 and PC3 were not associated with frailty. CONCLUSION: Our results suggest that anemia in patients with frailty is driven by inflammation rather than being disease-related or solely the result of micronutrient deficiencies.

Male Sex and Ageing are Independent Risk Factors for Sarcopenia Stage in Patients With Chronic Kidney Disease Not Yet on Dialysis.

BACKGROUND: The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD. METHODS: The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance. RESULTS: Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001). CONCLUSIONS: This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.

Prenatal and progressive coenzyme Q10 administration to mitigate muscle dysfunction in mitochondrial disease.

BACKGROUND: ADCK genes encode aarF domain-containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult-onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid ß-oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ10, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention. METHODS: We used Adck2 heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests. RESULTS: We demonstrated that Adck2 heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). Adck2 heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ10 could mitigate these embryonic defects. Heterozygous Adck2 mice also showed a decrease in myogenic cell differentiation, with more severe consequences in 'aged' mice (41.63% smaller) (P < 0.01). Consequently, heterozygous Adck2 mice displayed accelerated muscle wasting associated with ageing in muscle structure (P < 0.05), muscle function (less grip strength capacity) (P < 0.001) and muscle mitochondrial respiration (P < 0.001). Furthermore, progressive CoQ10 administration conferred protective effects on mitochondrial function (P < 0.0001) and skeletal muscle (P < 0.05). CONCLUSIONS: Our work uncovered novel aspects of CoQ deficiencies, revealing defects during embryonic development in mammals for the first time. Additionally, we identified the gradual establishment and progression of the deleterious Adck2 mouse phenotype. Importantly, CoQ10 supplementation demonstrated a protective effect when initiated during development.

The effectiveness of unsupervised home-based exercise for improving lower extremity physical function in older adults in Western and Eastern cultures: a systematic review and meta-analysis.

BACKGROUND: Ageing leads to decreased physical function, which can impact independent living and raise health risks, increasing demand on healthcare resources. Finding affordable and accessible exercise to improve physical function is necessary for a population seemingly resistant to strength and balance training in leisure settings. This review aimed to evaluate whether unsupervised home-based exercises improve lower extremity function in older adults. METHODS: We systematically searched for randomised controlled trials (RCTs) and cluster RCTs investigating unsupervised home-based exercises' effects on physical function in older adults through English and Mandarin databases. Studies' methodological quality was assessed using the Cochrane's Risk of Bias Tool. Meta-analyses were conducted on lower extremity functions outcomes. RESULTS: Of the 6791 identified articles, 10 English studies (907 participants) were included, 8 studies (839 participants) were used for final meta-analysis, with no Mandarin studies. Studies were largely based in Europe with mostly moderate risk of bias. Most interventions were multicomponent lasting 10-40 min/session, 3 times/week. Meta-analysis showed no statistically significant differences in 5 sit-to-stand (p = 0.05; I2 = 0%), maximal knee extension strength (p = 0.61; I2 = 71%), 10 m maximal walking speed (p = 0.22; I2 = 30%), timed-up-to-go (p = 0.54; I2 = 0%), and short physical performance battery (p = 0.32; I2 = 98%) between exercise and control groups. CONCLUSIONS: This meta-analysis suggests that unsupervised home-based exercise programmes have little impact on lower extremity functions in older adults. This review is limited by the small number of included studies, sample sizes, and high heterogeneity. There is a need to understand why this format lacks efficacy, and design more beneficial home-based exercise programmes.

Practice improves older adults' attentional control and prospective memory more than HD-tDCS: a randomized controlled trial.

Frontal and parietal brain regions are involved in attentional control and prospective memory. It is debated, however, whether increased or decreased activity in those regions is beneficial for older adults' task performance. We therefore aimed to systematically modulate activity in those regions using high-definition transcranial direct current stimulation. We included n = 106 healthy adults (60-75 years old, 58% female) in a randomized, double-blind, and sham-controlled study. We evaluated task performance twice in the laboratory and at home and additionally assessed heart rates. Participants received cathodal, anodal, or sham stimulation of the left or right inferior frontal lobe, or the right superior parietal lobe (1 mA for 20 min). Performance improved at visit two in laboratory tasks but declined in at-home tasks. Stimulation did not modulate performance change in laboratory tasks but prevented decline in at home-tasks. Heart rates increased at visit two but only when right inferior frontal lobe activity was inhibited. Repeating a task seems more beneficial than stimulation for laboratory tasks. This might be different for at-home tasks. Inhibiting right frontal brain function increases heart rates, possibly due to a modulation of the frontal-vagal brain-heart axis.

Frailty in Diabetic Population: A Study From Northern India.

Introduction Frailty, a key issue in geriatric health, signifies heightened vulnerability due to the decline in various physiological systems, exacerbated by conditions such as diabetes. Diabetes and frailty together lead to significant disabilities and higher mortality, necessitating early screening and targeted interventions. The relationship between frailty and diabetes remains under-researched, prompting this study to explore their association in individuals over 50 years of age using the Edmonton Frail Scale (EFS). Methods and materials The study was an observational cross-sectional study conducted at MM Institute of Medical Sciences & Research (MMIMSR), Mullana, India, among 102 diabetic and 100 non-diabetic individuals aged more than 50 years, with data collected through interviews using a pre-validated proforma. Frailty was assessed using the EFS, categorizing patients into fit, vulnerable, and various levels of frailty based on their scores. Results The study found a higher prevalence and severity of frailty among diabetic individuals (61.8%) compared to non-diabetics (29%), with frailty being more pronounced across all age groups and both genders in diabetics. The severity of frailty increased with the duration of diabetes but showed no significant correlation with glycemic control (HbA1c). Strengths and limitations The study prospectively collected data, including middle-aged participants starting from age 50, and uniquely used the EFS to assess frailty in diabetic patients, excluding those with other chronic diseases (end-stage renal disease (ESRD), malignancy, etc.). However, limitations included a small sample size, recruitment from a single institution in India, and some EFS questions being less relevant to the Indian diabetic population. Conclusion The study found a 61.8% prevalence of frailty in diabetics compared to 29% in non-diabetics, with frailty being more severe and positively correlated with the duration of diabetes but not with glycemic control (HbA1c).

An anatomical study of thenar and hypothenar soft tissue thickness in men and women.

We hypothesized that reduced thenar soft tissue thickness may be a risk factor for distal radial fractures. We assessed MRI scans of the wrist in 78 adults. The 51 men had significantly higher palmar soft tissue thickness compared to the 27 women, even after adjusting for hand size.Level of evidence: IV.

Taurine/chenodeoxycholic acid ratio as a potential serum biomarker for low vitamin B12 levels in humans.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

Considerations across multiple stakeholder groups when implementing fall prevention programs in the acute hospital setting: a qualitative study.

BACKGROUND: Falls in hospital remain a common and costly patient safety issue internationally. There is evidence that falls in hospitals can be prevented by multifactorial programs and by education for patients and staff, but these are often not routinely or effectively implemented in practice. Perspectives of multiple key stakeholder groups could inform implementation of fall prevention strategies. METHODS: Clinicians of different disciplines, patients and their families were recruited from wards at two acute public hospitals. Semi-structured interviews and focus groups were conducted to gain a broad understanding of participants' perspectives about implementing fall prevention programs. Data were analysed using an inductive thematic approach. RESULTS: Data from 50 participants revealed three key themes across the stakeholder groups shaping implementation of acute hospital fall prevention programs: (i) 'Fall prevention is a priority, but whose?' where participants agreed falls in hospital should be addressed but did not necessarily see themselves as responsible for this; (ii) 'Disempowered stakeholders' where participants expressed feeling frustrated and powerless with fall prevention in acute hospital settings; and (iii) 'Shared responsibility may be a solution' where participants were optimistic about the positive impact of collective action on effectively implementing fall prevention strategies. CONCLUSION: Key stakeholder groups agree that hospital fall prevention is a priority, however, challenges related to role perception, competing priorities, workforce pressure and disempowerment mean fall prevention may often be neglected in practice. Improving shared responsibility for fall prevention implementation across disciplines, organisational levels and patients, family and staff may help overcome this.

Dementia risk prediction modelling in low- and middle-income countries: current state of evidence.

Dementia is a leading cause of death and disability with over 60% of cases residing in low- and middle-income countries (LMICs). Therefore, new strategies to mitigate risk are urgently needed. However, despite the high burden of disease associated with dementia in LMICs, research into dementia risk profiling and risk prediction modelling is limited. Further, dementia risk prediction models developed in high income countries generally do not transport well to LMICs suggesting that context-specific models are instead needed. New prediction models have been developed, in China and Mexico only, with varying predictive accuracy. However, none has been externally validated or incorporated variables that may be important for predicting dementia risk in LMIC settings such as socio-economic status, literacy, healthcare access, nutrition, stress, pollutants, and occupational hazards. Since there is not yet any curative treatment for dementia, developing a context-specific dementia prediction model is urgently needed for planning early interventions for vulnerable groups, particularly for resource constrained LMIC settings.

Gene co-expression networks reveal sex-biased differences in musculoskeletal ageing.

Aging is a universal and progressive process involving the deterioration of physiological functions and the accumulation of cellular damage. Gene regulation programs influence how phenotypes respond to environmental and intrinsic changes during aging. Although several factors, including sex, are known to impact this process, the underlying mechanisms remain incompletely understood. Here, we investigate the functional organization patterns of skeletal muscle genes across different sexes and ages using gene co-expression networks (GCNs) to explore their influence on aging. We constructed GCNs for three different age groups for male and female samples, analyzed topological similarities and differences, inferred significant associated processes for each network, and constructed null models to provide statistically robust results. We found that each network is topologically and functionally distinct, with young women having the most associated processes, likely due to reproductive tasks. The functional organization and modularity of genes decline with age, starting from middle age, potentially leading to age-related deterioration. Women maintain better gene functional organization throughout life compared to men, especially in processes like macroautophagy and sarcomere organization. The study suggests that the loss of gene co-expression could be a universal aging marker. This research offers insights into how gene organization changes with age and sex, providing a complementary method to analyze aging.

Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.

This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.

Defining an ageing-related pathology, disease or syndrome: International Consensus Statement.

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability.

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder.

A scoping review of the impact of ageing on individual consumers' insurance purchase intentions.

Recently, the phenomenon of population ageing and its impact on the insurance industry has garnered increasing global attention. However, a notable gap in scholarly research persists in understanding the nuanced effects of ageing on consumer behaviour and insurance purchase intentions. This study maps the current academic evidence on how ageing influences individual consumers' insurance decisions. Using a scoping review methodology aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews and Joanna Briggs Institute guidelines, 44 articles out of 1082 from four databases-Web of Science, Scopus, ScienceDirect, and Emerald Insight-are reviewed. The results reveal a rising interest in this research area, with China emerging as a significant contributor. The focus is predominantly on Theory of Planned Behavior, quantitative methods, questionnaire survey, regression analysis, older population, and general health insurance. Variables capturing the impact of ageing, beyond demographic information, include family-related, risk-related, and expectation-related factors. This study highlights the current state of research on ageing's effect on insurance purchase intentions and offers valuable insights and directions for future research.