Accelerated Aging Research Articles

The influence of strong social ties on the choice of long-term care model for middle-aged and older adults in China.

With the acceleration of population aging in China, the care of middle-aged and older adults has become the focus of social attention. As China is an "acquaintance society," strong social relations play an important role in residents' access to information and resource allocation, which has an impact on the choice of long-term care models for middle-aged and older adults. Therefore, based on the 19,728 samples from the 2018 CHARLS Phase I data, an empirical analysis was conducted using a logistic dichotomous model, which showed that both kinship (p < 0.01) and friendship (p < 0.01) among social relationships positively influenced the choice of social care models for middle-aged and older adults. The analysis of the heterogeneity showed that the choice of long-term care models was significantly influenced by strong social relationships in the central and western regions and rural areas (p < 0.01). On the basis of this, the transmission mechanism of strong social relationships was further analyzed in conjunction with the further construction of the SIRS Contagion Model, which was used to describe the information transmission process. The results showed that residents who attached importance to strong social ties were more likely to incur medical transfer expenditure, thus further increasing their own demand for the formal care model. The policy implications of this study are to promote the coordinated development of long-term formal care and strong social relations, to further promote the socialization of the formal care model while relying on traditional family care, and to build a multi-level and diversified long-term care system for middle-aged and older adults.

Community and domestic violence are associated with DNA methylation GrimAge acceleration and heart rate variability in adolescents

ABSTRACT Background: Cumulative exposure to violence can change the regulation of epigenetic and physiological markers. Although violence has been associated with accelerated cellular aging, little is known about associations with cardiac autonomic activity. Objective: The current study aimed to investigate the relationship of exposure to community and domestic violence (CDV) with vagal activity and epigenetic aging acceleration. Methods: A total of 86 adolescents (57% female) were evaluated and interviewed at two time-points in São Gonçalo (2014–2019), a Brazilian city with high levels of violence. Exposure to CDV was assessed in both time-points. GrimAge acceleration was calculated from saliva DNA methylation using Infinium HumanMethylation450K (Illumina) collected in the first assessment. Heart rate variability (HRV) was collected during two stress tasks at the second assessment. Results: The exposure to violence witnessed or directly experienced at home and in the community increased significantly (t = 4.87, p < .01) across two-time points, and males had reported higher violence exposure (t = 2.06, p = .043). Violence at 1st assessment was significantly associated with GrimAge acceleration (B = .039, p value = .043). Violence at both assessments were associated with HRV measured during the narration of the worst trauma (traumaHRV) (B = .009, p value = .039, and B = .007, p value = .024, 1st and 2nd assessment respectively). GrimAge acceleration was significantly associated with traumaHRV (B = .043, p value = .049), and HRV measured during a 3D roller coaster video (B = .061, p value = .024). Conclusions: We found relevant evidence that experiencing violence during adolescence is associated with epigenetic aging and stress-related vagal activity. Understanding these factors during this period could contribute to the development of early interventions for health promotion. HIGHLIGHTS Higher exposure to Community and domestic violence is associated with increased GrimAge acceleration. Higher GrimAge acceleration is associated with increased stress-related vagal activity. Exposure to community and domestic violence increased significantly over time.

Connecting the Gut Microbiota and Neurodegenerative Diseases: the Role of Bile Acids.

With the acceleration of global population aging, neurodegenerative diseases (NDs) will become the second leading cause of death in the world, which seriously threatens human life and health. Alzheimer's disease and Parkinson's disease are the most common and typical NDs. The exact mechanisms of the NDs occurrence and development remain unclear, which may be related to immune, oxidative stress, and abnormal aggregation of pathogenic proteins. Studies have suggested that gut microbiota (GM) influences brain function and plays an important role in regulating emotional and cognitive function. Recently, bile acids (BAs) have become the "star molecule" in the microbiota-gut-brain (MGB) axis research. BAs have been reported to exert anti-inflammatory, antioxidant, and neuroprotective activities in NDs. However, the role of BAs in the connection between GM and the central nervous system (CNS) is still unclear. In this review, we will review the possible mechanisms of BAs between GM and NDs and explore the function of BAs to provide ideas for the prevention and treatment of NDs in the future.

Aging Mitigation for Battery Energy Storage System in Electric Vehicles

Battery energy storage systems (BESS) have been extensively investigated to improve the efficiency, economy, and stability of modern power systems and electric vehicles (EVs). However, it is still challenging to widely deploy BESS in commercial and industrial applications due to the concerns of battery aging. This paper proposes an integrated battery life loss modeling and anti-aging energy management (IBLEM) method for improving the total economy of BESS in EVs. The quantification of BESS aging cost is realized by a multifactorial battery life loss quantification model established by capturing aging characteristics from cell acceleration aging tests.Meanwhile, a charging event analysis method is proposed to deploy the built life loss model in vehicle BESS management. Two BESS active anti-aging vehicle energy management models: vehicle to grid (V2G) scheduling and plug-in hybrid electric vehicle (PHEV) power distribution, are further designed, where the battery life loss quantification model is used to generate the aging cost feedback signals. The performance of the developed method is validated on a V2G peak-shaving simulation system and a hybrid electric vehicle. The work in this paper presents a practical solution to quantify and mitigate battery aging costs by optimizing energy management strategies and thus can further promote transportation electrification.

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES

BackgroundAlthough tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown. MethodsData were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association. ResultsThe association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (β=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food. ConclusionsThe association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.

Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age

Brain aging may accelerate after rodents reach middle age. However, the endogenous mediator that promotes this acceleration is unknown. We predict that the mediator may be expressed after an organism reaches middle age and dysregulates mitochondrial function. In the neurons of wild-type Drosophila (flies), we observed that mitochondria were fragmented in aged flies, and this fragmentation was associated with mitochondrial calcium overload. In a previous study, we found that mitochondrial fragmentation induced by calcium overload was reversed by the loss of Vimar, which forms a complex with Miro. Interestingly, Vimar expression was increased after the flies reached middle age. Overexpression of Vimar in neurons resulted in premature aging and mitochondrial calcium overload. In contrast, downregulation of Vimar in flies older than middle age promoted healthy aging. As the mouse homolog of Vimar, RAP1GDS1 expression was found to be increased after mice reached middle age; RAP1GDS1-transgenic and RAP1GDS1-knockdown mice displayed similar responses to flies with overexpressed and reduced Vimar expression, respectively. This research provides genetic evidence of a conserved endogenous mediator that promotes accelerated brain aging.

Abstract 5757: Breast cancer diagnosis and treatment associated with acceleration of biological aging over time in a racially diverse cohort of women

Abstract Leukocyte DNA methylation (DNAm) at individual sites across the genome can be used to construct measures of biological age. Positive age acceleration—when biological age is older than chronological age—is associated with higher risk of age-associated diseases. Recent adjuvant therapy is reported to increase age acceleration, but the longer-term effects of a breast cancer diagnosis and treatment on age acceleration remain unknown. Here, we use blood samples collected at two timepoints to examine changes in age acceleration over time comparing women who did and did not develop breast cancer. Paired whole blood samples were drawn an average of 8 years apart (range: 5-11 years) in a sample of non-Hispanic White and Black (Hispanic and non-Hispanic) women. DNAm was profiled using Infinium MethylationEPIC BeadChips. Approximately half the women were diagnosed and treated for breast cancer between blood draws (cases; n= 190, baseline mean age= 57) whereas the other half remained breast cancer-free (controls; n= 227, baseline mean age= 56). Longitudinal changes in three age acceleration metrics were compared to determine whether an intervening breast cancer diagnosis and treatment was associated with trajectories in biological aging. On average, the cases were diagnosed with breast cancer 3.5 years after the initial blood draw and 4 years before the second blood draw. Among the cases, 36% were treated with chemotherapy, 65% with radiation therapy, and 70% with hormonal therapies; 45% of the cases received two types of therapy, and 13% received all three. Compared to women who remained cancer-free, women diagnosed and treated for breast cancer had increases in age acceleration over time as measured by PhenoAgeAccel (adjusted standardized mean difference (β)= 0.13, 95% CI: 0.00, 0.26), GrimAgeAccel (β= 0.13, 95% CI: 0.03, 0.24), and DunedinPACE (β= 0.35, 95% CI: 0.23, 0.48). The associations did not vary by timing of diagnosis between the blood draws or race; however, women diagnosed with estrogen receptor (ER) negative tumors appeared to experience faster increases in age acceleration than women diagnosed with ER positive tumors (GrimAgeAccel; ER negative β= 0.27, 95% CI: 0.07, 0.47; ER positive β= 0.10, 95% CI: -0.01, 0.21; P-interaction= 0.14). To investigate the impact of different types of breast cancer therapies, associations were examined using a case-only design. In models that simultaneously included chemotherapy, radiation therapy and hormone therapy, radiation therapy had the strongest associations with accelerated biological aging as measured by PhenoAgeAccel (β= 0.38, 95% CI: 0.18, 0.58), GrimAgeAccel (β= 0.27, 95% CI: 0.09, 0.45), and DunedinPACE (β= 0.25, 95% CI: 0.03, 0.47). We find that years after the initial diagnosis, breast cancer survivors have significantly accelerated biological aging; treatment modalities may differentially influence these rates. Citation Format: Jacob K. Kresovich, Katie M. O'Brien, Zongli Xu, Clarice R. Weinberg, Dale P. Sandler, Jack A. Taylor. Breast cancer diagnosis and treatment associated with acceleration of biological aging over time in a racially diverse cohort of women. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5757.

Field Emergence Test in Relation to Laboratory Seed Quality Tests of Sweet Corn Seed

High quality seeds of sweet corn will lead to high productivity. The quality of seeds can be known through germination testing. The field emergence test is one of seed quality testing with approach to a new method of quality testing in the field. The aims to study seed testing with the approach of field emergence method and finds out its relationship with the germination and vigor tests. This research used randomized complete block design (RCBD) with seven replications on each variety. Field emergence test was carried out by observing the number of open leaves and plant height while laboratory seed quality tests were assessed using standard germination test and accelerated ageing (AA) vigor test. The result showed that the field emergence test observed at 14 days after planting (DAP) gave a clear distinction of normal and abnormal plants, with a criteria normal plant had a criterion 3-4 open leaves and 16.9 ± 2.9 cm in plant height while abnormal had less than 3 leaves and short plant height. Field emergence percentage was calculated by the number of normal plants. There was a correlation at each time of observation of field emergence with germination and vigor tests result.

Pulsed magnetic field increases the effect of ultraviolet C radiation and thermal shock in aged yeasts

The study of the effects of the magnetic field (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple effects described to date, there are few published articles that study the combined effect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing effect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifies the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no effect.

Research on the Influence of Pension Insurance on the Chinese Elderlys Subjective Well-Being Based on Maslow's Hierarchy of Needs

The acceleration of population aging is a basic national condition in China. To ensure the living condition of the elderly is a strategic issue. Whether pension insurance plays a role in promoting the subjective well-being of the elderly has attracted widespread attention. This paper explores the degree and mechanism of the influence of current pension insurance programs in China on the subjective well-being of the Chinese elderly. The research significance of this paper lies in helping to provide a theoretical basis for relevant policy recommendations in the future. On this basis, this paper searches the literature on CNKI for research materials. Combined with their research questions, 21 articles from the past 20 years are selected to analyze the influence mechanism of pension insurance on the subjective well-being of the elderly, using Maslow's hierarchy of needs as the theoretical basis. The results show that pension insurance has a certain contribution to the subjective well-being of the elderly, acting in economic, psychological, and social aspects, respectively.

Cellular Senescence and Frailty in Transplantation.

To summarizes the literature on cellular senescence and frailty in solid-organ transplantation and highlight the emerging role of senotherapeutics as a treatment for cellular senescence. Solid-organ transplant patients are aging. Many factors contribute to aging acceleration in this population, including cellular senescence. Senescent cells accumulate in tissues and secrete proinflammatory and profibrotic proteins which result in tissue damage. Cellular senescence contributes to age-related diseases and frailty. Our understanding of the role cellular senescence plays in transplant-specific complications such as allograft immunogenicity and infections is expanding. Promising treatments, including senolytics, senomorphics, cell-based regenerative therapies, and behavioral interventions, may reduce cellular senescence abundance and frailty in patients with solid-organ transplants. Cellular senescence and frailty contribute to adverse outcomes in solid-organ transplantation. Continued pursuit of understanding the role cellular senescence plays in transplantation may lead to improved senotherapeutic approaches and better graft and patient outcomes.

The Mental Health Status and Influencing Factors of the Elderly in Nursing Homes

The base of the elderly population in China is increasing year by year, and the acceleration of population aging has led to more attention to the psychological problems of the elderly. It is also imperative to discuss the mental health status of the elderly population in current nursing homes. The paper discusses the current psychological status of the elderly in nursing homes, points out various factors that currently plague their mental health, and proposes countermeasures for improving their mental health in the future, providing a reference for related research.

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia.

Background: Along with acceleration of population aging, the increasing prevalence of sarcopenia has posed a heavy burden on families as well as society. In this context, it is of great significance to diagnose and intervene sarcopenia as early as possible. Recent evidence has indicated the role of cuproptosis in the development of sarcopenia. In this study, we aimed to seek the key cuproptosis-related genes that can be used for identification and intervention of sarcopenia. Methods: The GSE111016 dataset was retrieved from GEO. The 31 cuproptosis-related genes (CRGs) were obtained from previous published studies. The differentially expressed genes (DEGs) and Weighed gene co-expression network analysis (WGCNA) were subsequently analyzed. The core hub genes were acquired by the intersection of DEGs, WGCNA and CRGs. Through logistic regression analysis, we established a diagnostic model of sarcopenia based on the selected biomarkers and was validated in muscle samples from GSE111006 and GSE167186. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed on these genes. Furthermore, the gene set enrichment analysis (GSEA), and immune cell infiltration were also conducted on the identified core genes. Finally, we screened the potential drugs targeting the potential biomarkers of sarcopenia. Results: A total of 902 DEGs and WGCNA containing 1,281 significant genes were preliminarily selected. Intersection of DEGs, WGCNA and CRGs yielded four core genes (PDHA1, DLAT, PDHB, and NDUFC1) as potential biomarkers for the prediction of sarcopenia. The predictive model was established and validated with high AUC values. KEGG pathway and Gene Ontology biological analysis indicated these core genes may play a crucial role in energy metabolism in mitochondria, oxidation process, and aging-related degenerative diseases. In addition, the immune cells may be involved in the development of sarcopenia through mitochondrial metabolism. Finally, metformin was identified as a promising strategy of sarcopenia treatment via targeting NDUFC1. Conclusion: The four cuproptosis-related genes PDHA1, DLAT, PDHB and NDUFC1 may be the diagnostic biomarkers for sarcopenia, and metformin holds great potential to be developed as a therapy for sarcopenia. These outcomes provide new insights for better understanding of sarcopenia and innovative therapeutic approaches.

Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder.

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

Downregulation of Lysosome-Associated Membrane Protein-2A Contributes to the Pathogenesis of COPD.

Macroautophagy plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the role of chaperone-mediated autophagy (CMA) has not been investigated. We investigated if and how CMA is involved in the pathogenesis of COPD. We measured the level of lysosome-associated membrane protein-2A (LAMP-2A), which is a critical component of CMA that functions as a receptor for cytosolic substrate proteins, in total lung tissues and primary human bronchial epithelial cells (HBECs) from healthy never smokers, smokers, and COPD patients. We assessed the effects of LAMP-2A knock-down on cigarette smoke extract (CSE)-induced aging, cell cycle arrest, and apoptosis in BEAS-2B cells and the expression levels of apoptosis hallmarks in primary HBECs and lung tissue sections. We found that the protein levels of LAMP-2A in lung homogenates and primary HBECs from smokers and COPD patients were lower than those from never smokers. In addition, its level in primary HBECs was negatively correlated with years of smoking. CSE caused degradation of LAMP-2A protein via the lysosomal pathway by activating macroautophagy. Knock-down of LAMP-2A markedly enhanced CSE-induced expression of senescence markers such as p16, p21, p27, and p53. G2/M cell cycle arrest, up-regulation of cyclin B1, and apoptosis in BEAS-2B cells. Apoptosis was increased in CSE-treated primary HBECs and in lung tissues from smokers and COPD patients. Cigarette smoke-induced down-regulation of LAMP-2A is involved in acceleration of aging and apoptosis of lung epithelial cells, which might at least partially contribute to COPD pathogenesis.

Study on early warning treatment of senile depression in community based on artificial intelligence model

BackgroundIn recent years, with the acceleration of population aging in China, the number of elderly people with depression is increasing. Artificial intelligence models and data analysis have sound applications in the early warning and treatment of the elderly with depression in the community by finding the elderly with depression timely and carrying out early warning treatment for them.Subjects and Methods50 elderly people with depression, from two communities of equal size, were randomly selected to participate in the experiment. Among them, one community adopts routine management and treatment, and the other community conducts early-warning treatment based on an artificial intelligence model and data analysis. The former and the latter were used as the observation group and the intelligent group respectively. All the elderly were evaluated according to the Geriatric Depression Scale (GDS) before and 6 months after the experiment.ResultsThe GDS scores of the elderly in the observation group and the intelligent group before and after the experiment are shown in Table 1. The GDS scores of the observation group and the intelligent group are close before and after the experiment from Table 1. Six months after the experiment, the GDS scores of the intelligent group are significantly lower than that of the observation group. In this experiment, P &lt; 0.0 indicates that the difference is statistically significant.Table 1.GDS score results of the two groups of elderly before and after the experimentGroupProjectGDS score before the experimentGDS score after theexperimentObservation groupScore17.18±1.4514.71±1.13t0.1251.234P0.0340.039Intelligent groupScore16.31±1.2710..28±0.97t0.2431.314P0.0190.028ConclusionsAccording to statistics, the incidence rate of depression in the elderly can reach 10%, so it is necessary to strengthen the early warning and treatment of depression symptoms in the elderly. The artificial intelligence model and data analysis can help find the depressive symptoms of the elderly in the community as early as possible, and help take measures to carry out early warning treatment, thereby improving the depressive situation.AcknowledgementThe research is supported by: Provincial key platforms and major scientific research projects of Guangdong universities “Building an intelligent community public welfare platform based on blockchain (No. 2021ZDZX3004)”.

The Association of Physical Activity Behaviors and Patterns With Aging Acceleration: Evidence From the UKBiobank.

Prior evidence suggests that physical activity may reduce the risk of multiple diseases and mortality. However, whether and how physical activity affects the aging process remains largely unexplored. We included 284479 UK Biobank participants and computed leukocyte telomere length (LTL) deviation (ie, the difference between genetically determined and observed LTL) and biological age acceleration (defined as the discrepancy between the phenotypic age of a person and the average phenotypic age in the cohort of individuals with the same age and sex) as the indexes for aging acceleration. Linear and logistic models were used to estimate the associations of self-reported physical activity items and patterns (identified by principal component analysis), as well as accelerometer-assessed physical activity, with aging acceleration. Analyses of physical activity patterns indicated, a higher level of adherence to activity patterns predominated by strenuous sports, other exercises, walking for pleasure, heavy and light housework, and public transportation use was associated with a lower risk of aging acceleration, whereas a higher level of adherence to patterns predominated by job-related activities was associated with a higher risk of aging acceleration. Analysis among 62418 participants with accelerometer-measured physical activity corroborated these results. Physical activity, such as strenuous sports and other exercises in leisure time and the use of public transportation, was associated with reduced biological aging. Besides highlighting the importance of engaging in physical activity for healthy aging, our results provide further evidence for the beneficial effect of physical activity on the telomere attrition process.

Accelerated epigenetic aging in older adults with HIV disease: associations with serostatus, HIV clinical factors, and health literacy.

The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives on all four indicators. Within the PWH sample, higher levels of epigenetic aging acceleration were moderately associated with lower current CD4 count, AIDS diagnoses, higher scores on the Veterans Aging Cohort Study Index, and lower telomere values. Higher epigenetic aging acceleration indices were also associated with lower health literacy among PWH. PWH experience accelerated aging as measured by a series of epigenetic clocks, which may be linked to immune compromise and risk of all-cause mortality. Health literacy may be a modifiable target for mitigating the risk of accelerated aging among older PWH.

Clinical Epigenomic Explanation of the Epidemiology of Cannabinoid Genotoxicity Manifesting as Transgenerational Teratogenesis, Cancerogenesis and Aging Acceleration.

As global interest in the therapeutic potential of cannabis and its' derivatives for the management of selected diseases increases, it is increasingly imperative that the toxic profile of cannabinoids be thoroughly understood in order to correctly assess the balance between the therapeutic risks and benefits. Modern studies across a number of jurisdictions, including Canada, Australia, the US and Europe have confirmed that some of the most worrying and severe historical reports of both congenital anomalies and cancer induction following cannabis exposure actually underestimate the multisystem thousand megabase-scale transgenerational genetic damage. These findings from teratogenic and carcinogenic literature are supported by recent data showing the accelerated patterns of chronic disease and the advanced DNA methylation epigenomic clock age in cannabis exposed patients. Together, the increased multisystem carcinogenesis, teratogenesis and accelerated aging point strongly to cannabinoid-related genotoxicity being much more clinically significant than it is widely supposed and, thus, of very considerable public health and multigenerational impact. Recently reported longitudinal epigenome-wide association studies elegantly explain many of these observed effects with considerable methodological sophistication, including multiple pathways for the inhibition of the normal chromosomal segregation and DNA repair, the inhibition of the basic epigenetic machinery for DNA methylation and the demethylation and telomerase acceleration of the epigenomic promoter hypermethylation characterizing aging. For cancer, 810 hits were also noted. The types of malignancy which were observed have all been documented epidemiologically. Detailed epigenomic explications of the brain, heart, face, uronephrological, gastrointestinal and limb development were provided, which amply explained the observed teratological patterns, including the inhibition of the key morphogenic gradients. Hence, these major epigenomic insights constituted a powerful new series of arguments which advanced both our understanding of the downstream sequalae of multisystem multigenerational cannabinoid genotoxicity and also, since mechanisms are key to the causal argument, inveighed strongly in favor of the causal nature of the relationship. In this introductory conceptual overview, we present the various aspects of this novel synthetic paradigmatic framework. Such concepts suggest and, indeed, indicate numerous fields for further investigation and basic science research to advance the exploration of many important issues in biology, clinical medicine and population health. Given this, it is imperative we correctly appraise the risk-benefit ratio for each potential cannabis application, considering the potency, severity of disease, stage of human development and duration of use.

A Systematic Review on the Potential Acceleration of Neurocognitive Aging in Older Cancer Survivors.

As survival rates increase, more emphasis has gone to possible cognitive sequelae in older cancer patients, which could be explained by accelerated brain aging. In this review, we provide a complete overview of studies investigating neuroimaging, neurocognitive, and neurodegenerative disorders in older cancer survivors (>65 years), based on three databases (Pubmed, Web of Science and Medline). Ninety-six studies were included. Evidence was found for functional and structural brain changes (frontal regions, basal ganglia, gray and white matter), compared to healthy controls. Cognitive decline was mainly found in memory functioning. Anti-hormonal treatments were repeatedly associated with cognitive decline (tamoxifen) and sometimes with an increased risk of Alzheimer's disease (androgen deprivation therapy). Chemotherapy was inconsistently associated with later development of cognitive changes or dementia. Radiotherapy was not associated with cognition in patients with non-central nervous system cancer but can play a role in patients with central nervous system cancer, while neurosurgery seemed to improve their cognition in the short-term. Individual risk factors included cancer subtypes (e.g., brain cancer, hormone-related cancers), treatment (e.g., anti-hormonal therapy, chemotherapy, cranial radiation), genetic predisposition (e.g., APOE, COMT, BDNF), age, comorbidities (e.g., frailty, cognitive reserve), and psychological (e.g., depression, (post-traumatic) distress, sleep, fatigue) and social factors (e.g., loneliness, limited caregiver support, low SES). More research on accelerated aging is required to guide intervention studies.