Accelerated Aging Research Articles

Cinética de secagem e qualidade fisiológica de sementes de jiló

ABSTRACT The drying process is paramount for maintaining seed quality, where the temperature during this process directly influences germination and vigor, especially for vegetable species harvested with high moisture content. This research aimed to determine and model the drying curves of S. aethiopicum (cultivar Tinguá-verde-claro) seeds at temperatures of 35, 38, 41, and 44 ºC, as well as to evaluate the physiological quality of the seeds after drying. A completely randomized design was used, with four drying temperatures (35, 38, 41, and 44 ºC) and four replicates. Nine mathematical models were fitted using the non-linear regression analysis by the Gauss-Newton method, and the goodness of fit was assessed based on the magnitude of the coefficient of determination (R2), chi-square test (χ2), relative mean error (P), and estimated mean error (SE). Seed quality was evaluated by germination test (G), electrical conductivity (EC), and accelerated aging (AA). The Modified Midilli model best represents the drying curves of S. aethiopicum seeds at the studied temperatures. Seeds with higher germination and vigor, meaning lower electrical conductivity values and higher germination rates after accelerated aging, are achieved through drying at 35 and 38 ºC.

The environmental impact on aging: Insights from buccal mucosa and molecular biomarkers

Buccal epithelial cells serve as a primary barrier against the inhalation and ingestion of harmful substances, working alongside immune system cells such as natural killer cells to protect the body from health-damaging factors. These epithelial cells can also be used as an alternative tissue source for monitoring the genotoxic effects of external factors such as chemical exposure. This assessment can be performed using molecular biomarkers of aging, which reflect biological age and indicate cellular aging acceleration due to internal and external damage factors, such as environmental hazards. In contrast to chronological age, which merely reflects the passage of time, biological age accounts for individual variation in aging processes. Molecular biomarkers are crucial for distinguishing between normal and pathological processes in the body and for identifying the effects of external factors such as chemical exposures. The identification of specific biomarkers enhances the ability to detect and monitor adverse biological responses and accelerated aging. This review aims to highlight the routes through which environmental hazards enter the body, the application of buccal epithelial cells in assessing genetic modifications, and the introduction of potential molecular biomarkers. However, further research is necessary to elucidate the roles of these biomarkers in determining aging rates and individual variability. Understanding their implications may also help identify new therapeutic targets for preventing premature aging, treating age-related diseases, and developing potential treatments.

Ouabain Ameliorates Alzheimer’s Disease-Associated Neuropathology and Cognitive Impairment in FAD4T Mice

Background: Alzheimer’s disease (AD) is a common clinical neurodegenerative disorder, primarily characterized by progressive cognitive decline and behavioral abnormalities. The hallmark pathological changes of AD include widespread neuronal degeneration, plaques formed by the deposition of amyloid β-protein (Aβ), and neurofibrillary tangles (NFTs). With the acceleration of global aging, the incidence of AD is rising year by year, making it a major global public health concern. Due to the complex pathology of AD, finding effective interventions has become a key focus of research. Ouabain (OUA), a cardiac glycoside, is well-known for its efficacy in treating heart disease. Recent studies have also indicated its potential in AD therapy, although its exact mechanism of action remains unclear. Methods: This study integrates bioinformatics, multi-omics technologies, and in vivo and in vitro experiments to investigate the effects of OUA on the pathophysiological changes of AD and its underlying molecular mechanisms. Results: This study analyzed the expression of the triggering receptor expressed on myeloid cells 2 (TREM2) across different stages of AD using bioinformatics. Serum samples from patients were used to validate soluble TREM2 (sTREM2) levels. Using an Aβ1-42-induced microglial cell model, we confirmed that OUA enhances the PI3K/AKT signaling pathway activation by upregulating TREM2, which reduces neuroinflammation and promotes the transition of microglia from an M1 proinflammatory state to an M2 anti-inflammatory state. To evaluate the in vivo effects of OUA, we assessed the learning and memory capacity of FAD4T transgenic mice using the Morris water maze and contextual fear conditioning tests. We used real-time quantitative PCR, immunohistochemistry, and Western blotting to measure the expression of inflammation-associated cytokines and to assess microglia polarization. OUA enhances cognitive function in FAD4T mice and has been confirmed to modulate microglial M1/M2 phenotypes both in vitro and in vivo. Furthermore, through bioinformatics analysis, molecular docking, and experimental validation, TREM2 was identified as a potential target for OUA. It regulates PI3K/Akt signaling pathway activation, playing a crucial role in OUA-mediated M2 microglial polarization and its anti-inflammatory effects in models involving Aβ1-42-stimulated BV-2 cells and FAD4T mice. Conclusions: These findings indicate that OUA exerts anti-neuroinflammatory effects by regulating microglial polarization, reducing the production of inflammatory mediators, and activating the PI3K/Akt signaling pathway. Given its natural origin and dual effects on microglial polarization and neuroinflammation, OUA emerges as a promising therapeutic candidate for neuroinflammatory diseases such as AD.

A Biometric Identification for Multi-Modal Biomedical Signals in Geriatric Care

With the acceleration of global population aging, the elderly have an increasing demand for home care and nursing institutions, and the significance of health prevention and management of the elderly has become increasingly prominent. In this context, we propose a biometric recognition method for multi-modal biomedical signals. This article focuses on three key signals that can be picked up by wearable devices: ECG, PPG, and breath (RESP). The RESP signal is introduced into the existing two-mode signal identification for multi-mode identification. Firstly, the features of the signal in the time–frequency domain are extracted. To represent deep features in a low-dimensional feature space and expedite authentication tasks, PCA and LDA are employed for dimensionality reduction. MCCA is used for feature fusion, and SVM is used for identification. The accuracy and performance of the system were evaluated using both public data sets and self-collected data sets, with an accuracy of more than 99.5%. The experimental data fully show that this method significantly improves the accuracy of identity recognition. In the future, combined with the signal monitoring function of wearable devices, it can quickly identify individual elderly people with abnormal conditions, provide safer and more efficient medical services for the elderly, and relieve the pressure on medical resources.

Per- and poly-fluoroalkyl substances (PFAS) accelerate biological aging mediated by increased C-reactive protein

Unhealthy biological aging is related to higher incidence of varied age-related diseases, even higher all-cause mortality. Previous small sample size study suggested that Per- and poly-fluoroalkyl substances (PFAS) was associated with biological aging, but the evidence of exposure-response relationships, potential effect modifiers, and potential mediators were not investigated. Therefore, we conducted a cross-sectional analysis of national study including 14, 865 adults in the US from 8 survey cycles of NHANES from 2003 to 2018, to investigate the associations of PFAS compounds in body serum, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), with biological aging. Generalized linear models showed that higher human exposure to PFAS was associated with accelerated biological aging. Importantly, human exposure to PFOA, PFOS, PFNA, and PFHxS with detected level (above 0.10 ng/mL) was associated with an average of 3.3 year (95 %CI: 2.7, 3.9, P < 0.001), 14.9 year (95 %CI: 7.2, 22.7, P < 0.001), 10.9 years (95 %CI: 3.9, 17.7, P < 0.001), and 8.8 years (95 %CI: 4.8, 12.9, P < 0.001) of biological aging acceleration. Cubic spline models indicated exposure-response relationships where there was no safe threshold of PFAS level regarding harms to human healthy aging. The weighted sum regression model found the significant associations of PFAS compound mixture with biological aging acceleration, and PFOA was the dominant contributor among 4 PFAS compounds. Mediation analysis suggested that C-reactive protein, one of the inflammation biomarkers, might play as mediator in PFAS-induced accelerated biological aging, but not Triglyceride-glucose index. In summary, our study suggests that the effects of PFAS on biological aging acceleration should be of concern and more action plans to address their negative impact on human health should be launched.

Examining epigenetic aging in the post-mortem brain in attention deficit hyperactivity disorder.

Mathematical algorithms known as "epigenetic clocks" use methylation values at a set of CpG sites to estimate the biological age of an individual in a tissue-specific manner. These clocks have demonstrated both acceleration and delays in epigenetic aging in multiple neuropsychiatric conditions, including schizophrenia and neurodevelopmental disorders such as autism spectrum disorder. However, no study to date has examined epigenetic aging in ADHD despite its status as one of the most prevalent neurodevelopmental conditions, with 1 in 9 children having ever received an ADHD diagnosis in the US. Only a handful of studies have examined epigenetic age in brain tissue from neurodevelopmental conditions, with none focused on ADHD, despite the obvious relevance to pathogenesis. Thus, here we asked if post-mortem brain tissue in those with lifetime histories of ADHD would show accelerated or delayed epigenetic age, as has been found for other neurodevelopmental conditions. We applied four different epigenetic clocks to estimate epigenetic age in individuals with ADHD and unaffected controls from cortical (anterior cingulate cortex, N = 55) and striatal (caudate, N = 56) post-mortem brain tissue, as well as peripheral blood (N = 84) and saliva (N = 112). After determining which epigenetic clock performed best in each tissue, we asked if ADHD was associated with altered biological aging in corticostriatal brain and peripheral tissues. We found that a range of epigenetic clocks accurately predicted chronological age in all tissues. We also found that a diagnosis of ADHD was not significantly associated with differential epigenetic aging, neither for the postmortem ACC or caudate, nor for peripheral tissues. These findings held when accounting for comorbid psychiatric diagnoses, substance use, and stimulant medication. Thus, in this study of epigenetic clocks in ADHD, we find no evidence of altered epigenetic aging in corticostriatal brain regions nor in peripheral tissue. We consider reasons for this unexpected finding, including the limited sampling of brain regions, the age range of individuals studied, and the possibility that processes that accelerate epigenetic age may be counteracted by the developmental delay posited in some models of ADHD.

A residence time-based concept for modeling and analyzing the impact of diffusion on auto-ignition processes with thermal stratification

A meticulous definition of the residence time (also referred to as the fluid age) in the context of auto-ignition in a thermally stratified gas has demonstrated that the age can be considered as a level-set function, which allows the tracking of a self-ignition front propagating. In order to avoid the difficulty of defining the boundary and initial conditions for this age, which can be seen as fluid birth, a normalized age is introduced. Meticulous derivation of the equation revealed additional terms related to the scalar dissipation rates and the gradient in the composition space of the auto-ignition delay. To validate this model equation, two canonical configurations were proposed: one representing a hot spot self-igniting with significant thermal diffusion and the other where a self-ignition front propagates at an almost constant speed. The analysis, based on the normalized age of the particles, reveals the impact of thermal diffusion on the acceleration or deceleration of particle aging. In certain instances, a particle rejuvenation mechanism through thermal diffusion has been identified. Furthermore, this work demonstrates the capacity of the normalized residence time field to map transitions between auto-ignition and laminar flame. Finally, the different cases studied were classified in an auto-ignition/diffusion diagram based on three non-dimensional characteristic numbers, which highlighted five combustion regimes.

Exploration of the Characteristics of Elderly-Driver-Involved Single-Vehicle Hit-Fixed-Object Crashes in Pennsylvania, USA

With the acceleration of population aging, the elderly driving safety issue is increasingly prominent. Method: With the crash data of Pennsylvania from 2010 to 2019, this study exclusively discusses features of single-vehicle hit-fixed-object crashes (SVHFOCs), one of the most common and deadliest crash types for elderly drivers. Results: Firstly, we demonstrate that elderly drivers are much more likely to be injured and killed than young drivers in SVHFOCs by checking crash consequences. The descriptive analysis indicates that elderly drivers have very different crash features from young drivers. They are found to drive with more caution in many aspects, such as more low-speed local travels, fewer illegal behaviors, fewer nighttime travels, etc. Then, a logistic regression model is built to find the factors significantly influencing the severity of SVHFOCs from driver, vehicle, roadway, and environment. The estimation results indicate that female sex, not wearing a seatbelt, DUI, rural area, and SUV involvement tend to be associated with more severe SVHFOCs. Additionally, illumination, weather, and road type could also significantly affect crash severity. Especially, SVHFOCs in adverse weather, in dark conditions, and at intersections are found to be less severe, which implies that elderly drivers might drive more carefully in complex environments. Practical Applications: These findings are expected to provide new insights for agencies in formulating customized measures to prevent elderly drivers from being involved in SVHFOCs.

Acceleration of brain aging after small-volume infarcts.

Previous studies have shown that stroke patients exhibit greater neuroimaging-derived biological "brain age" than control subjects. This difference, known as the brain age gap (BAG), is calculated by comparing the chronological age with predicted brain age and is used as an indicator of brain health and aging. However, whether stroke accelerates the process of brain aging in patients with small-volume infarcts has not been established. By utilizing longitudinal data, we aimed to investigate whether small-volume infarctions can significantly increase the BAG, indicating accelerated brain aging. A total of 123 stroke patients presenting with small-volume infarcts were included in this retrospective study. The brain age model was trained via established protocols within the field of machine learning and the structural features of the brain from our previous study. We used t-tests and regression analyses to assess longitudinal brain age changes after stroke and the associations between brain age, acute stroke severity, and poststroke outcome factors. Significant brain aging occurred between the initial and 6-month follow-ups, with a mean increase in brain age of 1.04 years (t = 3.066, p < 0.05). Patients under 50 years of age experienced less aging after stroke than those over 50 years of age (p = 0.245). Additionally, patients with a National Institute of Health Stroke Scale score >3 at admission presented more pronounced adverse effects on brain aging, even after adjusting for confounders such as chronological age, sex, and total intracranial volume (F 1,117 = 7.339, p = 0.008, η 2 = 0.059). There were significant differences in the proportional brain age difference at 6 months among the different functional outcome groups defined by the Barthel Index (F 2,118 = 4.637, p = 0.012, η 2 = 0.073). Stroke accelerates the brain aging process, even in patients with relatively small-volume infarcts. This phenomenon is particularly accentuated in elderly patients, and both stroke severity and poststroke functional outcomes are closely associated with accelerated brain aging. Further studies are needed to explore the mechanisms underlying the accelerated brain aging observed in stroke patients, with a particular focus on the structural alterations and plasticity of the brain following minor strokes.

Ambient fine particulate matter and its constituents may exacerbate the acceleration of aging in adults

Both ambient fine particulate matter (PM2.5) and aging are important urban concerns. However, the associations between PM2.5 constituents and the acceleration of aging (AA) remain unclear. We included 16,051 adults (aged 25–80 years) with 19,252 medical observations in Taiwan during 2008−2017. 2-year average PM2.5 and its five major constituents were assessed using a two-stage machine learning model at a resolution of 1 km2. AA was determined by the difference between the Klemera–Doubal biological age and chronological age. A linear mixed model (LMM) with inverse probability weights was used to examine the associations between AA and air pollution. In a semi-randomized study design, we applied a post-matching LMM to assess the impacts of changes in air pollution exposure on AA. Each interquartile range increase in ambient PM2.5, SO4-2, NO3–, NH4+, organic matters (OM), and black carbon (BC) was associated with a 0.20 (95 %confidence interval [CI]: 0.17–0.24), 0.19 (0.15–0.23), 0.14 (0.11–0.18), 0.21 (0.17–0.24), 0.22 (0.19–0.26) and 0.25 (0.21–0.28) year increase in AA, respectively. BC was generally associated with the greatest increase in AA as compared to other constituents. We did not find evident thresholds in their concentration–response associations. Participants exposed to increased levels of PM2.5, SO4-2, NO3–, NH4+, OM, and BC experienced an increase in AA of 0.11 (−0.07–0.29), 0.20 (0.02–0.39), 0.15 (−0.02–0.33), 0.12 (−0.07–0.31), 0.24 (0.07–0.41), and 0.30 (0.07–0.52) years, respectively, compared to those exposed to decreased/unchanged levels. Long-term exposure to ambient PM2.5 and its constituents may accelerate biological aging among Chinese adults. Exposed to increased levels may further aggregate the aging process. This study suggests that reducing exposure to air pollution is beneficial, even for residents within moderately-to-highly polluted regions, such as Taiwan. Rigorous regulation of PM2.5 and its constituents may prevent the acceleration of biological age.

Leisure-time activities and disability among Chinese community-dwelling oldest old: evidence from the Chinese Longitudinal Healthy Longevity Study.

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

Periodontitis prevalence and acceleration of biological aging: Insights from NHANES 2009-2014 and Mendelian randomization study.

This study aimed to investigate the association of periodontitis with biological aging and to assess potential causality using Mendelian randomization (MR). A cross-sectional study with 9558 participants from the National Health and Nutrition Examination Survey (2009-2014) was conducted. Age acceleration (BioAgeAccel and PhenoAgeAccel) was calculated from clinical biomarkers and their discrepancies with chronological age. Two-sample MR analysis was performed using data from a large-scale genome-wide association study and UK Biobank. Periodontitis was associated with increased biological aging, with 0.57-year (95% CI: 0.28-0.86, p < .001) increases in BioAgeAccel and 0.41-year (95% CI: 0.04-0.78, p = .034) increases in PhenoAgeAccel. Subgroup analysis found significantly stronger associations in males for BioAgeAccele (PINTERACTION = .006), and pronounced associations in young adults (pinteraction = .023), individuals with normal body mass index (pinteraction = .015), and current smokers (pinteraction = .016) for PehonAgeAccel. MR analysis did not provide strong evidence for a causal effect of periodontitis on biological aging (BioAgeAccel: IVW β = 0.008, 95% CI: -0.018 to 0.034, p = .553 and PhenoAgeAccel: IVW β = 0.016, 95% CI: -0.042 to 0.074, p = .585). This study identified the association of periodontitis and its severity with accelerated aging, suggesting periodontal health could be a possible method in personalized preventive and therapeutic strategies of biological aging.

Childhood Adversity and Adolescent Epigenetic Age Acceleration: The Role of Adolescent Sleep Health.

We investigated how a dimension of early life adversity (ELA) capturing threat in the home relates to later epigenetic age acceleration in adolescence through sleep (duration, efficiency, and timing), to empirically test theoretical models suggesting the importance of sleep as a key mechanism linking ELA with poor health outcomes, and to expand the limited literature on sleep and epigenetic aging among youth. We utilized data from 861 participants from the Future of Families and Child Wellbeing Study (FFCWS) who participated in the actigraphy sub study at age 15. Sleep variables used were average total sleep time (TST), sleep efficiency (SE), and sleep onset timing. Home threat was determined at ages 3, 5, and 9 from parent reports on the Child Conflict Tactics Scale (CTS-PC), and epigenetic aging was measured through DNA methylation analyses of saliva samples collected at age 15. Higher levels of childhood home threat exposure were associated with less adolescent TST, lower SE, and later sleep onset timing. Adolescent SE and timing were associated with a faster pace of aging and epigenetic age acceleration. Sleep efficiency and timing mediated the link between childhood home threat exposure and adolescent epigenetic aging. Epigenetic embedding of childhood threat exposure in the home may occur through adversity-related sleep disturbances in adolescence. Findings warrant greater attention to pediatric sleep health in theoretical models of biological embedding of adversity and point to the examination of improving sleep health as a potential way to prevent adversity-related epigenetic age acceleration.

The association of psychological and trauma-related factors with biological and facial aging acceleration: evidence from the UK Biobank

BackgroundPsychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking.MethodsUsing data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models.ResultsWe observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the “Absence of trauma and psychopathology” cluster, the “adverse childhood experiences (ACEs) with psychopathology” cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 − 1.23] for biological and 1.52 [1.18 − 1.95] for facial aging acceleration), while no such association was observed for the “ACEs without psychopathology” cluster (1.04 [0.99 − 1.09] and 1.02 [0.84 − 1.24].ConclusionsOur study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals’ psychological resilience to prevent aging acceleration.

Omega-3 PUFAs slow organ aging through promoting energy metabolism

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator–activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid β-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

Gerotherapeutics: Aging Mechanism-based Pharmaceutical and Behavioral Interventions to Reduce Cancer Racial and Ethnic Disparities.

The central premise of this article is that a portion of the established relationships between social determinants of health and racial/ethnic disparities in cancer morbidity and mortality are mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions ("gerotherapeutics") to differentially improve the health of minoritized cancer survivors and reduce cancer disparities. These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging ("social determinants of aging"), with minoritized groups having accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than non-minoritized groups. Acceleration of biological aging can increase the risk, age of onset, aggressivity and/or stage of many adult cancers. There are also documented negative feedback loops whereby the cellular damage caused by cancer and its therapies act as drivers of additional biological aging. Together, these dynamic intersectional forces can contribute to differences in cancer outcomes between minoritized vs non-minoritized survivor populations. We highlight key targetable biological aging mechanisms with potential applications to reducing cancer disparities and discuss methodological considerations for pre-clinical and clinical testing of the impact of gerotherapeutics on cancer outcomes in minoritized populations. Ultimately, the promise of reducing cancer disparities will require broad societal policy changes that address the structural causes of accelerated biological aging and ensure equitable access to all new cancer control paradigms.

Exploring the anti-ovarian aging mechanism of He's Yangchao formula: Insights from multi-omics analysis in naturally aged mice

BackgroundThe rapid acceleration of female reproductive aging has become a major public health concern. He's Yangchao formula (HSYC), a compound comprising eight herbs, has demonstrated efficacy in enhancing ovarian function. Thus, an in-depth study of its anti-ovarian aging mechanism is required. PurposeTo evaluate the anti-ovarian aging effect of HSYC in naturally aged mice and investigate the underlying mechanism by analyzing the gut microbiota (GM), metabolome, and transcriptome. MethodsYoung and advanced maternal age (AMA) mice were selected for this study. Hematoxylin and eosin staining, fluorescence staining, western blotting, and qPCR analyses were used to detect the phenotypes associated with ovarian aging. Subsequently, analyses of the GM, transcriptome, and metabolome analyses were performed to explore the potential mechanisms of action of HSYC. Finally, in vivo and in vitro experiments were performed to verify potential therapeutic mechanisms. ResultsHSYC promoted follicular development in AMA mice and ameliorated age-related mitochondrial dysfunction, apoptosis, and defects in DNA damage repair. GM analysis revealed that HSYC treatment significantly increased the abundance of Akkermansia and Turicibacter. Transcriptome and metabolome analyses showed that HSYC might mitigate ovarian aging by regulating metabolic pathways, amino acid metabolism, glutathione metabolism, and the synthesis of pantothenic acid and coenzyme A. Combined transcriptomic and metabolomic analyses identified the glutathione metabolic pathway as the key pathway through which HSYC counteracts ovarian aging. Additional experimental verification confirmed that HSYC upregulated the glutathione metabolic genes GPX8, GSTA1, and GSTA4, increased glutathione-related products (GSH), and reduced ROS levels. ConclusionsHSYC exerts beneficial therapeutic effects on ovarian aging by regulating multiple endogenous metabolites, targets, and metabolic pathways, with an emphasis on its anti-ovarian aging effects through the glutathione metabolic pathway. These findings underscore the innovative potential of HSYC in addressing ovarian aging and offer a novel therapeutic approach that targets multiple biological pathways to improve the reproductive health of women with AMA..

The Relationship Between Central Obesity and Osteoarthritis in US Adults: The Mediating Role of Biological Aging Acceleration

Objective This study aims to investigate the association between central obesity and the risk of osteoarthritis, and the mediating role of biological age and biological aging advance in this relationship. Methods The study is based on data from the National Health and Nutrition Examination Survey (NHANES) for the years 2005–2018. Thirteen commonly used clinical traits were used to calculate the Klemera-Doubal method age (KDM-Age) and phenotypic age (Pheno-Age) as two measures of biological aging. Additionally, KDM-Age advance and Pheno-Age advance were calculated as two measures of biological aging advance. Weighted multivariable logistic regression was used to analyze the association between central obesity and the risk of osteoarthritis (OA). Mediation analysis was then applied to elucidate the role of biological aging and biological aging advance in this relationship. Results A total of 31,162 subjects aged ≥20 years were included in this study, of which 3,964 subjects reported having OA (14%). Compared to the Non-OA group, the OA group showed significantly higher proportions of central obesity, KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance. Compared to the Non-central obesity group, the central obesity group had higher KDM-Age, KDM-Age advance, PhenoAge, PhenoAge advance, and a higher risk of OA (p < 0.05). Additionally, higher KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance were positively correlated with the risk of OA (p < 0.05). Mediation analysis revealed that part of the association between central obesity and the risk of OA was mediated by KDM-Age, KDM-Age advance, PhenoAge, and PhenoAge advance (p < 0.05). Conclusion Central obesity increases the risk of OA, with part of this association being mediated by biological aging and biological aging advance.

The association between weekly exercise patterns and acceleration of aging: Evidence from a population-based study

BackgroundAcceleration of aging is a major challenge in public health. Previous studies have focused on the associations between specific types of exercise or overall levels of physical activity with accelerated aging, with less attention given to the weekly exercise patterns. ObjectiveTo explore the relationship between weekly exercise patterns and acceleration of aging among American adults. MethodsWe extracted data from the 2015–2018 National Health and Nutrition Examination Survey (NHANES), involving 9850 participants aged ≥20 with comprehensive records on exercise and phenotypic age. Hierarchical clustering categorized participants into three groups based on weekly exercise time and days: cluster 1 (Rare or No Exercise), cluster 2 (Moderate Frequency, Moderate Duration) and cluster 3 (Moderate Frequency, Long Duration). Acceleration of aging was defined as the phenotypic age advance >0. ResultsAfter full adjustment, weekly exercise time and days showed the significant non-linear negative correlation with accelerated aging. The risk of accelerated aging was lowest when weekly exercise days reached five and the weekly exercise time reached three hours. Both cluster 2 and cluster 3 were significantly negatively correlated with acceleration of aging. No significant differences were observed in the association with accelerated aging between cluster 2 and cluster 3. ConclusionsThese findings highlight the importance of targeted exercise programs for healthy aging. They also emphasize the need for public health initiatives to integrate regular physical activity into daily routines to improve the longevity and well-being of American adults.

Prenatal and early-life air pollutant exposure and epigenetic aging acceleration

BackgroundThis study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) Materials & methodsAir pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath’s clock, Horvath’s skin and blood clock, PedBE, and Wu’s clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. ResultsA total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 μg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath’s clock), respectively. An IQR increase in PM2.5 (4.76 μg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath’s clock) and 0.289 years of EAA (Wu’s clock). PM10 (4.30 μg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath’s clock (0.280 years) and EAA in Horvath’s skin and blood clock (0.163 years), respectively. ConclusionWe found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.