Search Results (535)

Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)—gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis—we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene–lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, p = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (INPP5D, ATG16L1, ATG7, AP3S1, OPTN, and VPS33A) were associated with SI in KoGES (p < 5 × 10⁻⁵), and ten SNPs (genes selected in KoGES plus RAB7A, ATG12, VPS33A, BECN1) reached genome-wide significance in UKBB (p < 5 × 10⁻⁸). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene–lifestyle interactions were observed for diet, physical activity, smoking, and alcohol (p < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. Full article

The effects of reproductive technologies, namely, artificial insemination (AI) and multiple ovulation embryo transfer (MOET), on the production, health, and longevity of Holstein–Friesian cows were evaluated. Data were obtained from the time period between 2017 and 2024 on a Hungarian dairy farm and consisted of 1783 cows (1544 AI and 239 MOET). Deep-frozen semen from identical bulls was used for both the AI and MOET groups. Disease incidence, productive life, and early-lactation milk production phenotypes were collected in these cows. MOET cows demonstrated significantly higher milk yield during the first 100 days of lactation but had a 43.9% greater risk of culling compared with AI cows (p < 0.05). Metabolic and reproductive disorders were the most common reasons for culling cows, with increased frequency of health issues correlating with higher culling risk ratios (p < 0.05). While MOET cows showed lower incidences of metabolic disorders, reproductive problems, and mastitis, their shorter productive lifespan likely limited overall disease exposure. Nevertheless, when MOET cows experienced illness, the impact was more severe, particularly in relation to metabolic issues (p < 0.05). These findings highlight trade-offs between improved genetic potential and health resilience in MOET-derived cows. Despite their higher productivity, their management may require greater health vigilance. This study offers practical insights for dairy producers in selecting reproductive strategies to balance genetic gain, herd health, and longevity under intensive production systems. Full article

Dental implants are a popular clinical procedure for the rehabilitation of fully and partially ede ntulous patients. There is long-term evidence that implant-supported dental prostheses represent a predictable treatment for replacing missing teeth. However, several types of complications may arise, which can compromise implant treatment outcome. Peri-implant disease is a growing biological complication, consisting of a progressive loss of supporting bone, associated with microbial biofilm and clinical inflammation. It represents a concern for clinicians and patients, having a negative impact on quality of life. This narrative review aimed at summarize the current knowledge on etiology, epidemiology, risk factors, and pathogenesis of peri-implant disease. It also focused on the diagnostic potential of active matrix metalloproteinase-8 (aMMP-8) in peri-implant sulcular fluid for assessing the status of peri-implant tissues and the risk of developing peri-implantitis. A literature search was conducted in PubMed and Scopus databases using search terms like: peri-implantitis, peri-implant biomarkers, aMMP-8, implant maintenance, risk assessment. Clinical studies, systematic reviews, meta-analysis and consensus papers published up to June 2025 were considered. Finally, based on the main factors involved in the onset and progression of peri-implant disease, a new protocol was conceived for determining the optimal implant maintenance scheduling for individual patients. The Biomarker-Guided Implant Maintenance (BGIM) protocol considers a few key parameters, among which aMMP-8 level, and proposes three categories associated with different levels of risk for peri-implantitis. The higher the risk, the more frequently a patient should undergo professional maintenance, to prevent peri-implant disease, with potential favorable effects on implant longevity. The proposed BGIM protocol, that requires prospective validation, represents a structured and clinically applicable biomarker-driven framework for individualizing implant maintenance scheduling by integrating real-time chairside quantification of aMMP-8 with established patient-related risk factors. Full article

Vascular ageing is a complex process marked by progressive endothelial dysfunction, chronic low-grade inflammation (“inflammageing”), and reduced regenerative capacity, driven in part by an imbalance between protective endothelial autophagy and cellular senescence characterized by a proinflammatory senescence-associated secretory phenotype (SASP). Disruption of this autophagy–senescence axis accelerates vascular inflammation, arterial stiffening, and atherogenesis. High-intensity interval training (HIIT), consisting of repeated bouts of near-maximal anaerobic effort with recovery periods, is widely used by both elite and recreational athletes and is increasingly recognized as an effective nonpharmacological strategy to enhance endothelial function, arterial elasticity, and mitochondrial biogenesis. However, excessively intense or poorly structured HIIT, particularly in the absence of adequate recovery or in individuals with underlying cardiometabolic or vascular vulnerability, may induce endothelial stress and promote maladaptive vascular remodelling, including calcification and plaque instability. These considerations underscore the need for refined individualized exercise prescription strategies that balance performance benefits with endothelial protection. Based on these observations, here, we introduce a novel conceptual framework, “shear dose–calibrated HIIT,” designed to understand and define an optimal shear dose capable of maximizing autophagic flux while minimizing SASP activation. Experimental and clinical evidence of HIIT-induced effects on flow-mediated dilation (FMD), pulse wave velocity (PWV), and redox biomarkers is presented, followed by the proposal of a biomarker panel for assessing autophagic flux and cellular senescence in peripheral samples (peripheral blood mononuclear cells (PBMCs), extracellular vehicles (EVs), and plasma). This integrative approach, which combines vascular mechanotransduction, redox biology, and autophagic signalling, provides a novel translational perspective on how individually calibrated HIIT can promote vascular longevity and reduce cardiometabolic risk associated with aging and metabolic syndrome. Full article

Background: Hyaluronic acid (HA) hydrogels are the most widely used injectable fillers for facial rejuvenation. A new generation of HA fillers crosslinked with poly(ethylene glycol) diglycidyl ether (PEGDE) has been developed to enhance cohesiveness, tissue integration, stability, and longevity while minimizing swelling and immunogenicity. Owing to their distinct viscoelastic properties, PEGDE-crosslinked HA fillers may require product-specific selection and adapted injection techniques. Objective: The objective of this study is to provide practical, expert-based recommendations for the safe and effective use of PEGDE-crosslinked HA hydrogels in facial aesthetic treatments. Methods: A multidisciplinary panel of nine Italian experts in aesthetic medicine, each with more than 15 years of experience using HA fillers, developed consensus recommendations based on clinical practice and available evidence. A pre-meeting questionnaire informed structured discussions during a face-to-face meeting held in Paris in January 2024. The nominal group technique was applied, with consensus defined as agreement by at least 80% of panel members. Results: Consensus was reached on product selection, injection planes, delivery devices, techniques, and typical treatment volumes for PEGDE-HA hydrogels across multiple facial regions, including the forehead, temples, midface, nasolabial folds, chin, jawline, and lips. Recommended injection techniques included microbolus, macrobolus, and retrograde linear threading, with placement ranging from superficial subcutaneous to supraperiosteal planes depending on the anatomical area and clinical indication. Typical injection volumes generally ranged from 0.1 to 0.5 mL per side. Optional ultrasound mapping was considered beneficial in selected high-risk or superficial procedures to improve anatomical safety. Conclusions: These expert consensus recommendations provide practical guidance for clinicians using PEGDE-crosslinked HA hydrogels in facial rejuvenation. Tailoring product characteristics to injection depth, technique, and regional anatomy may help optimize clinical outcomes and procedural safety. Future research priorities include prospective comparative studies with other crosslinking technologies, standardized reporting of adverse events, long-term outcome registries, and further evaluation of ultrasound-guided injection strategies. Full article

The preservation of littoral zones faces escalating challenges from global thermal forcing and anthropogenic pressure, particularly in vulnerable basins like the Mediterranean. This research proposes an expanded Coastal Vulnerability Index to assess 253 km of beaches across the Valencian Community (Spain), integrating sediment durability parameters for the first time. Methodologically, an arithmetic mean of ten physical, biotic, and sedimentological indicators was employed, including a novel Sediment Quality Classification Index (SQCI) derived from accelerated particle wear tests as a key resilience indicator. Results reveal that 40.9% of the coastline exhibits high or very high risk, reaching critical levels in the province of Valencia due to key driving factors such as a 91.8% proportion of fine sediments and the severe degradation of its dune systems. Conversely, the presence of Posidonia oceanica meadows in Alicante acts as a key resilience factor. It is possible to conclude that the mechanical quality of sediment is a determinant for the longevity of protection measures, highlighting the necessity of transitioning from rigid infrastructures towards ecosystem-based adaptation to enhance regional resilience. Full article

This critical integrative review reassesses the lipid paradigm by systematically mapping 380 influential trials and cohort studies on cholesterol, saturated fats, and statins in relation to cardiovascular and cognitive outcomes. The evidence base reveals a nearly even split between studies supporting and challenging LDL-centric causality, alongside pervasive methodological flaws, including reliance on surrogate lipid markers, ecological inferences, residual confounding, and industry-related reporting biases. Trial-generation comparisons and structured risk-of-bias assessment (ROB 2, ROBINS-I) repeatedly show that substantial pharmacological LDL reductions do not consistently yield proportional reductions in myocardial infarction, stroke, or all-cause mortality. Integrating Mendelian randomization with clinical and metabolomic data, the review advances a Critical Window Hypothesis in which LDL is necessary but not sufficient for atherogenesis, exerting dominant causal influence during early and midlife plaque initiation, while inflammatory, oxidative, and hemodynamic factors become primary drivers in advanced disease. Metabolomic studies of extreme longevity and late-life cohorts demonstrate that bile acids, steroid metabolites, and low-glycemic metabolic profiles—not total cholesterol—better predict survival and cognitive preservation, and that higher LDL in the oldest-old often associates with lower mortality and dementia risk. These findings challenge universal LDL-centric policies and support lifestyle medicine strategies prioritizing systemic metabolic optimization over isolated cholesterol targets. Full article

Background/Objectives: The Mediterranean diet (MeDiet) is widely recognised as one of the healthiest dietary patterns, associated with reduced risk of chronic diseases and increased longevity. Beyond its nutritional components, the Mediterranean lifestyle encompasses a broader set of culturally rooted behaviours that may contribute to its health benefits. This study aimed to assess adherence to the Mediterranean diet and lifestyle using the MEDLIFE index and to explore how dietary and lifestyle behaviours cluster into coherent behavioural patterns. Methods: We conducted an observational study among undergraduate students in health and sports sciences and a comparison group of older adults, using an anonymous questionnaire based on the MEDLIFE index. Data were analysed using a pattern-based approach combining network analysis and score-based enrichment to characterise behavioural profiles associated with different levels of Mediterranean lifestyle adherence. Results: Network-based analyses revealed a high degree of internal coherence among dietary and lifestyle behaviours traditionally associated with the Mediterranean lifestyle. In particular, dietary restraint behaviours (e.g., limitation of sugar, salt, and snack consumption) systematically co-occurred with recommended Mediterranean food choices, indicating that positive intake and self-regulation are part of a unified behavioural framework. Score-based stratification confirmed these patterns at the individual level, with low adherence characterised by the absence of key Mediterranean components and unhealthy lifestyle habits, and high adherence reflecting an integrated profile combining healthy food choices, moderation, and lifestyle practices. Conclusions: Adherence to the Mediterranean diet reflects a holistic lifestyle strategy rather than a collection of isolated dietary behaviours. These findings support public health approaches that target coherent behavioural patterns, integrating diet, self-regulation, and lifestyle habits, rather than focusing exclusively on individual dietary components. Full article

Preeclampsia (PE) has traditionally been regarded as a pregnancy-limited hypertensive disorder; however, accumulating evidence increasingly positions it as a pivotal early-life vascular stress test that manifests underlying vulnerabilities and accelerates biological aging. Women with a history of PE exhibit a heightened susceptibility to premature-onset multi-systemic diseases, specifically cardiovascular, ovarian, renal, and metabolic decline. This suggests that PE acts as a catalyst for accelerated aging, driven by shared pathophysiological pathways that represent common mechanisms of systemic senescence. This review provides a comprehensive analysis of the epidemiological links and pathogenic drivers underpinning accelerated systemic aging following PE, with a specific focus on the cardiovascular-ovarian axis. Epidemiological data consistently demonstrate that women with prior PE exhibit significantly reduced anti-Müllerian hormone (AMH) levels, translating to an estimated 1.5-year acceleration in reproductive aging. In parallel, PE is associated with a twofold increase in lifetime cardiovascular disease (CVD) risk and the onset of chronic hypertension occurring an average of 7.7 years earlier. However, reconciling the phenotypic heterogeneity of PE and transcending the constraints of non-experimental designs are essential for firmly establishing this accelerated aging paradigm. At the molecular level, PE and ovarian aging converge on shared pathways—including mitochondrial dysfunction, oxidative stress, inflammation, and epigenetic dysregulation—collectively defining a distinct pathogenic ovarian–vascular aging axis. Proposed geroscience-based strategies advocate for refined risk stratification by incorporating molecular aging biomarkers—such as epigenetic clocks and inflammatory profiles—alongside conventional clinical indicators. This integrative framework facilitates the early identification of high-risk aging phenotypes, enabling targeted monitoring and timely interventions to preemptively modulate accelerated aging pathways. Pharmacological approaches within this framework emphasize the judicious repurposing of established agents, such as metformin, statins, and SGLT2 inhibitors, while emerging gerotherapeutics, including senolytics and senomorphics, provide a conceptual foundation for targeting the fundamental biological drivers of senescence. Although these geroprotective strategies, including the repurposing of established agents and the use of senolytics, offer innovative conceptual frameworks for targeting the fundamental drivers of senescence, they remain largely exploratory and require further clinical validation. Such strategies offer novel opportunities to shift the clinical focus from treating isolated comorbidities to modulating the shared molecular substrates of aging, ultimately promoting healthy aging and functional longevity in the elderly female population. Full article

Guaranteed annuity options (GAOs) allow policyholders to convert accumulated funds into life annuities at maturity at a guaranteed minimum rate. Thus, insurers are exposed to both investment and longevity risks. Accurate valuation of these long-term, survival-contingent contracts is essential for solvency assessment and risk management. Many existing approaches assume independence between interest rate and mortality risks. This paper develops a computationally efficient pricing framework for GAOs that jointly models interest and mortality rates as correlated stochastic processes with regime-switching dynamics governed by a finite-state continuous-time Markov chain. Model parameters are estimated using U.S. interest rates and cohort mortality data via quasi-maximum likelihood estimation. A semi-analytic valuation formula is derived based on the joint distribution of the underlying processes. Numerical results show that incorporating correlation and regime-switching materially increases GAO prices relative to conventional one-state models. The proposed semi-analytic approach delivers substantial computational advantages over standard Monte Carlo simulations. Sensitivity analysis further identifies the parameters most relevant for long-horizon pricing and solvency considerations. This highlights the practical relevance of the framework for managing longevity-linked guarantees under economic and demographic uncertainty. Full article

This paper presents a probabilistic, multi-layered framework designed to forecast the longevity and security of cryptographic systems under the dual pressures of classical and quantum computational threats. The model integrates thermodynamic decay analogies, stochastic transitions via Hidden Markov Models, and an adapted financial option pricing method to quantify cryptographic degradation, strategic risk, and transition readiness. This framework can guide standardization roadmaps, cipher retirement, or quantum-migration planning, guiding proactive, instead of reactive, crypto agility. Furthermore, it provides a quantitative methodology to complement the current opinions expressed in surveys, as well as a qualitative approach to cryptographic security risk projections. Full article

Chrysopa pallens Stephens (Neuroptera: Chrysopidae) is a key predatory species in cotton agroecosystems. This study investigated the prey-mediated sublethal effects of imidacloprid and nitenpyram at low concentrations (LC₂₀), on C. pallens when exposed via consumption of contaminated prey, assessing impacts on its development and predatory function. C. pallens is a key predatory species in cotton agroecosystems. This study investigated the prey-mediated sublethal effects of imidacloprid and nitenpyram (LC₂₀) on the developmental performance and predatory capacity of C. pallens. Leaf-dipping bioassays were used to assess the toxicity of imidacloprid and nitenpyram to Aphis gossypii Glover (Hemiptera: Aphididae). Age-stage, two-sex life table analysis was conducted to evaluate their subsequent effects on the life history traits and predation performance of C. pallens. Imidacloprid was more toxic to A. gossypii than nitenpyram. Sublethal exposure marginally prolonged larval development, but the effect was not statistically significant. Both insecticides significantly extended the pupal stage, with nitenpyram inducing a greater delay. Imidacloprid markedly increased adult longevity, and both compounds significantly reduced female fecundity. Imidacloprid also suppress predatory behavior more potently, decreasing daily adult consumption and reducing first-instar attack rates by approximately 30%. Although all treatments followed a Holling type II functional response, both insecticides increased handling time and reduced searching efficiency. Overall, imidacloprid primarily inhibited predatory performance, whereas nitenpyram more strongly prolonged development and reduced critical population growth parameters. These findings provide essential evidence for ecological risk assessment and for refining the incorporation of natural enemies into cotton integrated pest management (IPM) strategies. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder that is increasingly recognized as a systemic condition with profound implications for female reproductive potential. In addition to pelvic distortion and impaired folliculogenesis, growing evidence indicates that intrinsic alterations in oocyte morphology, mitochondrial function, and developmental competence contribute to infertility. The disease is driven by a multifactorial interplay of somatic mutations, epigenetic remodeling, immune dysregulation, and aberrant steroid signaling, which together create a pro-inflammatory, oxidative, and fibrotic microenvironment. Elevated cytokines, reactive oxygen species, and disrupted granulosa-cell function within the follicular niche impair meiotic progression, cytoplasmic maturation, and mitochondrial integrity, potentially accelerating oocyte aging and diminishing reproductive longevity. Epigenetic and post-transcriptional disturbances—including altered DNA methylation, histone modifications, and RNA-splicing defects—further reinforce estrogen dominance, progesterone resistance, and impaired decidualization, with downstream consequences for ovarian–endometrial communication. Although morphological abnormalities have been documented in oocytes from women with endometriosis, clinical outcomes remain heterogeneous, highlighting the need for integrative models that connect molecular alterations to functional reproductive endpoints. A deeper understanding of these mechanisms is essential for identifying biomarkers of oocyte competence and modifiable strategies—ranging from nutritional optimization to reduction of environmental risk factors—in clinical care to safeguard the reproductive potential of women with endometriosis. Full article

In recent decades, the rate of kidney transplantation has risen significantly, leading to better outcomes in terms of cardiovascular and overall mortality for patients with kidney failure. Although kidney transplantation represents the most effective therapeutic option, it is not devoid of the risk of failure. Immunological and non-immunological risk factors are involved. These factors often interact and may act synergistically, ultimately influencing graft longevity and patient survival. Both contribute to long-term transplant outcomes; however, non-immunological factors, representing a significant clinical challenge, will be the focus of our review. Of the numerous non-immunological risk factors, for clarity and to avoid overextending the discussion, only those most closely associated with chronic kidney disease have been considered: hypertension, anemia, diabetes mellitus, proteinuria, electrolyte and acid–base imbalances, and impaired bone mineralization. Hypertension is reported in approximately 90% of kidney transplant recipients, often related to immunosuppressive therapy and residual renal dysfunction, and it is strongly associated with reduced graft survival. Anemia affects approximately 20–51% of these patients, contributing to cardiovascular morbidity and a more rapid decline in graft function, as does pre-existing diabetes mellitus. Proteinuria has a prevalence ranging from 7.5% to 45%, depending on the established target, and is a significant negative prognostic factor. Metabolic complications are also frequent; for example, hyperkalemia has an incidence of 25–44%, and metabolic acidosis has a prevalence of 12–58%. In our review, each of these factors is analyzed in terms of clinical impact, etiopathogenic mechanism, and available therapeutic management. Full article

Background/Objectives. Ebstein’s anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4–5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report the oldest documented case of a 45-year-old female with the exceptionally rare combination of complete AVCD, EA, and right ventricular hypoplasia and to provide a concise review of these anomalies. Case presentation. Diagnosed in early childhood with a complete AVCD, pulmonary stenosis, and right ventricular (RV) hypoplasia, the patient underwent palliative surgical intervention with a modified Blalock–Taussig shunt at the age of 10 but did not receive subsequent regular follow-up. Over the ensuing 35 years, she remained largely untreated until presentation at 45 years of age with progressive exertional dyspnea, central cyanosis, and palpitations, corresponding to NYHA class III. Comprehensive multimodal imaging, including transthoracic echocardiography and cardiac magnetic resonance, revealed a complete AVCD with moderate-to-severe mitral regurgitation secondary to an anterior mitral leaflet cleft, severe tricuspid regurgitation, RV hypoplasia, and hallmark features of EA. Given the complex cardiac anatomy and the elevated surgical risk, the patient was considered inoperable, and a strategy of conservative management with multidisciplinary follow-up was implemented. Conclusions. This case highlights the exceptional longevity of a patient with the rare coexistence of complete AVCD, EA, and RV hypoplasia, surviving 45 years from diagnosis despite limited early intervention. It underscores the importance of lifelong follow-up in complex congenital heart disease and illustrates the role of multimodal imaging in assessing anatomy and guiding management when surgical options are high-risk or not feasible. Full article