Search Results (127)

Depression is one of the most prevalent mental health conditions in middle and late adulthood, contributing substantially to morbidity, mortality, and reduced quality of life. However, limited research has examined the mechanisms linking genetic predisposition and early protective environments to long-term mental health trajectories. Guided by a life course health development perspective, this study investigated how depression polygenic scores (G) and protective childhood family environments (E) interplay to shape depressive symptom trajectories from mid- to late adulthood. We analyzed longitudinal data of 14 waves from the Health and Retirement Study (1994–2020; N = 4817), estimating linear mixed-effects models of depressive symptoms using the validated CES-D scale. Early protective environments were measured by indicators of family structure stability, non-abusive and substance-free parenting, positive parent–child relationships, and parental support. Results showed that genetic predisposition and protective family environments jointly influence depression trajectories across the life course. Specifically, individuals with both low genetic risk and high environmental protection had the lowest depressive symptoms over time. Importantly, when only one favorable factor was present, protective family environments offered a stronger lifelong benefit than low genetic risk. These findings extend prior research by demonstrating that supportive childhood environments can mitigate genetic vulnerability, shaping healthier long-term mental health trajectories. This work underscores the need for early family-based interventions to reduce depression risk, enhance resilience, and promote longevity. Full article

This paper investigates the role of proportional reinsurance as a practical and flexible tool for managing demographic risk in life insurance, with a focus on its impact on both the Solvency Capital Requirement (SCR) and expected profitability. While much of the existing literature focuses on mortality modeling or longevity-linked reinsurance instruments, this paper proposes a novel framework for analyzing traditional proportional reinsurance structures within the Solvency II market-consistent valuation environment. The framework integrates proportional reinsurance into the valuation of liabilities and the calculation of Solvency Capital Requirement, beginning with an outline of cash flow structures and their valuation under Solvency II principles. A key contribution is the introduction and decomposition of the net of reinsurance Claims Development Result (CDR), which allows us to assess the dual impact of reinsurance on risk mitigation and profit transfer. Through numerical analysis, we show how proportional reinsurance can effectively reduce capital requirements while quantifying the trade-off in expected profit transferred to the reinsurance company, with insights into how different reinsurance treaties affect capital efficiency and profitability. Full article

Introduction and Aim: Renal transplant recipients face significant long-term graft and patient loss due to post-transplant malignancies. This study aimed to characterize post-transplant malignancies, determine mortality risk factors, and evaluate patient outcomes. Materials and Methods: This retrospective study included 2052 kidney transplant recipients who underwent transplantation between 1976 and 2019 at our institution, other national centers, or international facilities, and who had at least six months of follow-up. Regardless of the transplant center, all patients were followed exclusively at our nephrology department for post-transplant care. A comprehensive review of patient files was conducted, encompassing demographic data, malignancy type and treatment, mortality rates, tissue compatibility assessments, viral serology results, immunosuppression protocols, acute rejection history, and pre-transplant malignancies. The relationships between these variables and mortality were examined. Results: A total of 167 malignant events were observed in 163 patients out of 2052 renal transplant patients (7.9%). The female patients comprised 34.4% (n = 56) of the participants. Ages at transplantation and malignancy diagnosis had medians of 40.0 (13–72) and 50.0 (23–78) years, respectively. The leading malignancy was skin cancer at 30.0%, with Kaposi sarcoma at 11.3% and post-transplant lymphoproliferative disease at 10.6% following. Of the patients followed up, 58.9% (93 patients) had mortality. In univariate analysis, older age at transplant, older age at malignancy diagnosis, and male sex were associated with mortality; however, no independent predictors were identified in the multivariate model (all p > 0.05), likely due to sample size limitations and inter-variable collinearity. Mortality showed statistically significant associations (p < 0.05) with increased age at transplantation, increased age at malignancy diagnosis, and male gender. Conclusions: Post-transplant malignancies significantly compromise both graft longevity and patient survival. Particularly aggressive skin cancers demand heightened clinical vigilance. Early detection through regular dermatological screening, patient education, and timely biopsies must become integral to long-term transplant care protocols. Full article

Capital investment in longevity science—research targeting the biological processes of aging through interventions like cellular reprogramming, AI-driven drug discovery, and biological age monitoring—may create significant divergence between traditional actuarial projections and emerging mortality improvements. This paper examines how accelerating investment in life extension technologies affects mortality improvement trajectories beyond conventional actuarial assumptions, building on the comprehensive investment landscape analysis documented in “Investors in Longevity” supported by venture capital databases, industry reports, and regulatory filings. We introduce an Investment-Adjusted Mortality Model (IAMM) that incorporates capital allocation trends as leading indicators of mortality improvement acceleration. Under high-investment scenarios (annual funding of USD 15+ billion in longevity technologies), current insurance products may significantly underestimate longevity risk, creating potential solvency challenges. Our statistical analysis demonstrates that investment-driven mortality improvements—actual reductions in death rates resulting from new anti-aging interventions—could exceed traditional projections by 18–31% by 2040. We validate our model by backtesting historical data, showing improved predictive performance (35% reduction in MAPE) compared to traditional Lee–Carter approaches during periods of significant medical technology advancement. Based on these findings, we propose modified insurance structures, including dynamic mortality-linked products and biological age underwriting, quantifying their effectiveness in reducing longevity risk exposure by 42–67%. These results suggest the need for actuarial science to incorporate investment dynamics in response to the changing longevity investment environment detailed in “Investors in Longevity”. The framework presented provides both theoretically grounded and empirically tested tools for incorporating investment dynamics into mortality projections and insurance product design, addressing gaps in current risk management approaches for long-term mortality exposure. Full article

Background/Objectives: Primary prevention, germline, familial, or other pre- or post-diagnostic and standard treatment-elevated progression or recurrence risk and mitigating adverse events from systemic treatment are all clinical opportunities to reduce the risk of lethal prostate cancer. This review attempted to provide a practical and realistic consensus via an international committee of experts who, in general, harbor career-long experience in this discipline. Methods: A PubMed review primarily utilizing the latest meta-analyses, systematic reviews, and methodologically robust epidemiologic recent data adjusting for multiple confounding variables was conducted. The goal of this committee was to highlight tangible options for clinicians and patients. Results: Behavioral patterns and metrics known to reduce cardiovascular morbidity, mortality, and all-cause mortality (premature death) appear to prevent numerous lethal common cancers, including prostate cancer. This practical approach allows for the greatest probability of patient success since cardiovascular disease (CVD) is the primary cause of death in men with and without prostate cancer, and a notable source of morbidity and mortality in men with advanced disease due to systemic conventional treatment as well as the inflammatory contribution of cancer itself. Heart-healthy dietary patterns, exercise, healthy weight/waist circumference, eliminating tobacco, minimizing alcohol exposure, and other behaviors to reduce the risk of CVD should be prioritized. CVD-preventive medications, including aspirin, GLP-1 agonists, metformin, statins, etc., should receive attention to improve compliance for those that already qualify for these agents and to increase the probability of enhancing the quality and quantity of life. Dietary supplements do not have favorable data currently to espouse their utilization to prevent lethal prostate cancer but may have an ancillary role in mitigating some adverse effects of treatment. Conclusions: Remarkably, heart-healthy lifestyle changes, metrics, and promising repurposed medications known to reduce cardiovascular events, promote longevity, and improve mental health could simultaneously prevent lethal prostate cancer. This serendipitous association provides clinicians and their patients a higher probability of success, regardless of their prostate cancer pathway or circumstance. Full article

Male infertility is a prevalent condition affecting approximately 15% of couples worldwide. Recent evidence indicates that, beyond its immediate reproductive implications, male infertility may reflect broader health concerns. Large-scale cohort studies consistently show that men with poorer semen parameters have elevated all-cause mortality compared to fertile counterparts, with a dose-dependent pattern whereby more severe abnormalities correlate with a higher risk of early death. Proposed mechanisms linking infertility to reduced life expectancy encompass genetic, hormonal, and lifestyle factors. For instance, Klinefelter syndrome exemplifies a genetic cause of azoospermia that also predisposes to metabolic syndrome, diabetes, and certain malignancies. Low testosterone, a frequent finding in testicular dysfunction, is implicated in obesity, insulin resistance, and cardiovascular disease, all of which can shorten lifespan. Additionally, psychosocial stress and depression—commonly reported among infertile men—may contribute to health-compromising behaviors. Environmental exposures and socioeconomic factors further compound these risks. Collectively, these data underscore the importance of recognizing male infertility as an early indicator of potentially modifiable health vulnerabilities. A comprehensive evaluation of infertile men should therefore extend beyond fertility assessments to include screening for chronic diseases, hormonal imbalances, and mental health issues. Targeted surveillance for specific cancers (e.g., testicular and prostate) and early interventions—such as lifestyle modifications, appropriate hormonal therapies, and psychosocial support—can improve both reproductive outcomes and long-term well-being. Given these insights, male fertility assessment may serve as a valuable gateway to broader men’s healthcare, prompting proactive strategies that mitigate associated risks and potentially enhance longevity. Full article

Aging is the primary risk factor for chronic diseases such as cardiovascular disease, cancer, and dementia. However, chronological age alone fails to capture individual variability in aging trajectories and disease susceptibility. Recent advances in epigenetic clocks—DNA methylation-based models that estimate biological age—have opened new possibilities for personalized and preventive medicine. This review explores the clinical potential of epigenetic clocks and EpiScores, composite biomarkers that predict health risks and physiological status. We present a comparative evaluation of widely used epigenetic clocks, including Horvath, GrimAge, PhenoAge, and DunedinPACE, and summarize their predictive performance for mortality, cognitive decline, and cardiovascular outcomes. EpiScores linked to inflammation, glycemic control, and immunosenescence are highlighted as tools for stratified risk assessment. When integrated with multi-omics data and electronic health records, these measures enhance the precision of population health management. Special emphasis is placed on applications in longevity clinics and anti-aging clinics, community-based care, and national health checkup systems. We also explore global standardization efforts and ethical considerations, as well as Japan’s unique initiatives—including the “Aging Measurement” project at the Osaka-Kansai Expo 2025. Furthermore, we propose the development of a Global Health and Aging Index that integrates the biological, functional, and subjective dimensions of aging, aligned with the WHO concept of Intrinsic Capacity. In conclusion, epigenetic clocks and EpiScores represent transformative tools for shifting from reactive treatment to proactive health optimization, and from chronological to biological metrics in aging science and public health policy. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity. Full article

The analysis of cognitive trajectories is relatively underexplored in China. Furthermore, most previous studies examining the association between cognitive function and mortality have been limited to cross-sectional perspectives. This study aims to identify distinct cognitive trajectories and the corresponding influencing factors and investigate the impact of these trajectories on all-cause mortality in Chinese older adults. A total of 6232 subjects aged 65 years and above were drawn from the Chinese Longitudinal Healthy Longevity Survey. Growth mixture models were utilized to identify different cognitive trajectories, while Cox proportional hazards models were used to examine the association between the cognitive trajectories and all-cause mortality after adjusting for covariates. Four cognitive trajectories were identified: rapid decline group, slow decline group, low-level stable group, and high-level stable group. Some factors such as age, sex, and marital status were significantly associated with trajectories. Compared to the high-level stable group, adjusted hazard ratios and 95% confidence intervals (CIs) for the all-cause mortality were 3.87 (95% CI: 3.35–4.48), 1.41 (95% CI: 1.24–1.59), and 1.37 (95% CI: 1.18–1.58) for the rapid decline group, the slow decline group, and the low-level stable group, respectively, indicating that these three groups had a higher mortality risk. In summary, these findings facilitate the development of targeted health promotion measures, which have implications for reducing the social and economic burdens of cognitive decline. Full article

Wildfire activity in the western U.S. has highlighted the importance of effective management to address this growing threat. The Lookout Mountain Thinning and Fuels Reduction Study (LMS) is an operational-scale, long-term study of the effects of forest restoration and fuel reduction treatments in ponderosa pine (Pinus ponderosa Dougl. ex Laws.) and mixed-conifer forests in central Oregon, U.S. The broad objectives of the LMS are to examine the effectiveness and longevity of treatments on wildfire risk and to assess the collateral effects. Treatments include four levels of overstory thinning followed by mastication of the understory vegetation and prescribed burning. Stands were thinned to residual densities of 50, 75, or 100% of the upper management zone (UMZ), which accounts for site differences as reflected by stand density relationships for specific plant communities. A fourth treatment combines the 75 UMZ with small gaps (~0.1 ha) to facilitate regeneration (75 UMZ + Gaps). A fifth treatment comprises an untreated control (UC). We examined the causes and levels of tree mortality that occurred 2–9 years after treatments. A total of 391,292 trees was inventoried, of which 2.3% (9084) died. Higher levels of tree mortality (all causes) occurred on the UC (7.1 ± 1.9%, mean ± SEM) than on the 50 UMZ (0.7 ± 0.1%). Mortality was attributed to several bark beetle species (Coleoptera: Curculionidae) (4002 trees), unknown factors (2682 trees), wind (1958 trees), suppression (327 trees), snow breakage (61 trees), prescribed fire (19 trees), western gall rust (15 trees), cankers (8 trees), mechanical damage (5 trees), dwarf mistletoe (4 trees), and woodborers (3 trees). Among bark beetles, tree mortality was attributed to western pine beetle (Dendroctonus brevicomis LeConte) (1631 trees), fir engraver (Scolytus ventralis LeConte) (1580 trees), mountain pine beetle (Dendroctonus ponderosae Hopkins) (526 trees), engraver beetles (Ips spp.) (169 trees), hemlock engraver (Scolytus tsugae (Swaine)) (77 trees), and Pityogenes spp. (19 trees). Higher levels of bark beetle-caused tree mortality occurred on the UC (2.9 ± 0.7%) than on the 50 UMZ (0.3 ± 0.1%) which, in general, was the relationship observed for individual bark beetle species. Higher levels of tree mortality were attributed to wind on the 100 UMZ (1.0 ± 0.2%) and UC (1.2 ± 1.5%) than on the 50 UMZ (0.2 ± 0.02%) and 75 UMZ (0.4 ± 0.1%). Higher levels of tree mortality were attributed to suppression on the UC (0.5 ± 0.3%) than on the 50 UMZ (0.003 ± 0.002%) and 75 UMZ + Gaps (0.0 ± 0.0%). Significant positive correlations were observed between measures of stand density and levels of tree mortality for most causal agents. Tree size (diameter at 1.37 m) frequently had a significant effect on tree mortality, but relationships varied by causal agent. The forest restoration and fuels reduction treatments implemented on the LMS increased resistance to multiple disturbances. The implications of these and other results to the management of fire-adapted forests are discussed. Full article

The aging population is steadily increasing, with aging and age-related diseases serving as major risk factors for morbidity, mortality, and economic burden. Peanuts, known as the “longevity nut” in China, have been shown to offer various health benefits, with peanut skin extract (PSE) emerging as a key compound of interest. This study investigates the bioactive compound in PSE with anti-aging potential and explores its underlying mechanisms of action. Procyanidin A1 (PC A1) was isolated from PSE, guided by the K6001 yeast replicative lifespan model. PC A1 prolonged the replicative lifespan of yeast and the yeast-like chronological lifespan of PC12 cells. To further confirm its anti-aging effect, cellular senescence, a hallmark of aging, was assessed. In senescent cells induced by etoposide (Etop), PC A1 alleviated senescence by reducing ROS levels, decreasing the percentage of senescent cells, and restoring proliferative capacity. Transcriptomics analysis revealed that PC A1 induced apoptosis, reduced senescence-associated secretory phenotype (SASP) factors, and modulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The antioxidative capacity of PC A1 was also evaluated, showing enhanced resistance to oxidative stress in PC12 cells by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Moreover, PC A1 induced autophagy, as evidenced by an increase in fluorescence-labeled autophagic compartments and confirmation via Western blot analysis of autophagy-related proteins. In addition, the treatment of an autophagy inhibitor abolished the antioxidative stress and senescence-alleviating effects of PC A1. These findings reveal that PC A1 extended lifespans and alleviated cellular senescence by enhancing oxidative stress resistance and inducing autophagy, positioning it as a promising candidate for further exploration as a geroprotective agent. Full article

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants associated with various health risks; however, their relationship with all-cause mortality in individuals with diabetes remains unclear. A total of 1256 participants from the National Health and Nutrition Examination Survey (NHANES) were included to explore the association between seven PFAS compounds and all-cause mortality in diabetic patients. Preliminary logistic regression identified three PFAS compounds (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], and 2-(N-methyl-PFOSA) acetate acid [MPAH]) as significantly associated with mortality in the diabetic population. The optimal cut-off values for PFOS, PFOA, and MPAH were determined using the X-tile algorithm, and participants were categorized into high- and low-exposure groups. Kaplan–Meier survival curves and multivariable Cox proportional hazards regression models were used to assess the relationship between PFAS levels and mortality risk. The results showed that high levels of PFOS were significantly associated with increased all-cause mortality risk in diabetic patients (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.06–2.29), while PFOA and MPAH showed no significant associations. To explore mechanisms underlying the PFOS–mortality link, toxicogenomic analysis identified 95 overlapping genes associated with PFOS exposure and diabetes-related mortality using the Comparative Toxicogenomics Database (CTD) and GeneCards. Functional enrichment analysis revealed key biological processes, such as glucose homeostasis and response to peptide hormone, with pathways including the longevity regulating pathway, apoptosis, and p53 signaling pathway. Protein–protein interaction network analysis identified 10 hub genes, and PFOS was found to upregulate or downregulate their mRNA expression, protein activity, or protein expression, with notable effects on mRNA levels. These findings suggest that PFOS exposure contributes to increased mortality risk in diabetic patients through pathways related to glucose metabolism, apoptosis, and cellular signaling. Our study provides new insights into the association between PFAS and all-cause mortality in diabetes, highlighting the need for large-scale cohort studies and further in vivo and in vitro experiments to validate these findings. Full article

Sickle cell disease/trait (SCD/T) is the most common genetic blood disorder in the U.S., characterized by painful vaso-occlusive crises resulting in considerable morbidity and premature death. Advances in treatment have somewhat improved the quality of life and longevity. Therefore, people with SCD/T are now living into their reproductive years. However, pregnant individuals with SCD have a maternal mortality risk of up to 26 times higher than the national average. Individuals with sickle cell trait also have an increased risk of untoward maternal health outcomes. We sought to understand reproductive health concerns among women with SCD/T, through data collected from patients, caregivers, advocates, and healthcare professionals using key informant interviews and focus groups (N = 54). Audio recordings were transcribed verbatim, coded inductively, and analyzed thematically. Three major themes emerged: (1) the Dilemma of Love vs. Risk, (2) SCD/T Knowledge, and (3) the Mental and Emotional Toll of SCD/T. Reproductive concerns and experiences among women with SCD/T influence their mental health and social engagement. Programs are urgently needed that address the unique SCD/T reproductive health risks and communication and support needs. These include readily accessible, age-appropriate SCD/T reproductive health information, counseling, and engaging communication tools for women and their potential partners. Support requires a multidisciplinary approach. Full article

Background/Objectives: Hypercholesterolemia is commonly viewed as a risk factor for coronary heart disease; however, several studies have reported an inverse relationship between cholesterol levels and cardiovascular mortality, particularly in older adults. This “cholesterol paradox” challenges the conventional understanding of lipid metabolism. Despite often being dismissed as a result of reverse causality, the precise causes of this paradox remain poorly understood. This study aimed to investigate the potential existence of the cholesterol paradox in a long-lived population from central Sardinia, Italy. Methods: We recruited 168 baseline nonagenarians (81 males, 87 females) from the longevity Blue Zone area in 2018 and followed them until December 2024. The lipid profile was determined for all participants according to current guidelines, and its impact on survival was analyzed with Kaplan–Meier curves and Cox proportional hazards regression models. Results: The median total cholesterol was 199.5 (range 89–314) mg/dL in males and 202.5 (range 89–324) mg/dL in females. Survival time was significantly longer in participants with LDL cholesterol (LDL-C) above 130 mg/dL compared to that in nonagenarians with LDL-C lower than 130 mg/dL (3.82 ± 1.88 years vs. 2.79 ± 1.56 years, p < 0.0001). Cox regression analysis revealed a significant reduction in the hazard ratio (HR) for mortality in participants with mild hypercholesterolemia (LDL-C ≥ 130 mg/dL) compared to that in those with normal cholesterol (OR 0.600, 95%CI 0.405–0.891). Conclusions: In the long-lived population examined, the cholesterol paradox was unlikely to be a reflection of reverse causality. Our results challenge the common view that longevity is invariably associated with low cholesterol levels. Furthermore, moderate hypercholesterolemia does not preclude the oldest adult from attaining advanced ages, contrary to common belief. Full article

Pugs are a popular brachycephalic breed that suffer from multiple chronic disorders linked to their exaggerated phenotypic traits. The contribution of these disorders to early death and euthanasia have not been described and would add urgency to addressing these issues. This study used electronic patient records (EPR) from the Australian VetCompass programme to describe the demography, common causes and risk factors for Pug mortality. The EPR from 691 Pugs which died in a population of 7909 Pugs that received veterinary care over a 10-year period were analysed to determine the cause of death. The median age at death was 10 years. Male Pugs had lower probability of surviving than females (p = 0.02) and entire Pugs died earlier than neutered dogs. The top causes of mortality were Brachycephalic Obstructive Airway Syndrome (8.2%), seizures (6.7%) and degenerative spinal cord disorder (4.7%). Neurological causes (29.6%) were the most common cause of euthanasia whilst amongst non-assisted deaths, respiratory causes were most common (25%). Death from respiratory disorders was found across all age groups. These neurological and respiratory causes of death are linked to brachycephalic conformation and provide evidence for reform of showing and breeding standards to improve Pug welfare and longevity. Full article