Accelerated biological aging among chemical plant workers.

Chronic obstructive pulmonary disease (COPD) results from a complex interaction between genes and the environment, and occupational exposures are an underappreciated risk factor. Until now, little research attention has been paid to the potential impact of occupational risk factor exposure on the COPD in China. The aim of this retrospective study was to analyze the role of occupational risk factor exposure on the severity and progression of COPD for exploring new prevention strategies for this disease. This study adopted a random cluster-sampling method. Five grade-A tertiary hospitals that met the inclusion criteria were selected as the survey sites, and patients with COPD hospitalized in these hospitals from January 1, 2019, to December 31, 2019, were selected as the research subjects. Data of the patients diagnosed with COPD met the Global Initiative for Chronic Obstructive Lung Disease (2019) criteria and were collected from the computerized medical record databases. Among 4082 investigated COPD patients, 1063 (26%) were found to have occupational risk factor exposure history. The top 3 industries with a large COPD case number and a history of occupational risk factor exposure ranked in the order of agriculture (including farming, forestry, animal husbandry, and fishery), manufacturing, and mining. Further multivariate logistic regression analysis indicated that when setting a low exposure level as a reference, medium and high exposure levels were correlated with the severity of COPD (odds ratio values were 2.837 and 6.201, respectively, P < .05). Linear regression analysis showed that cumulative exposure to occupational risk factors was negatively correlated with the forced expiratory volume in 1-second percentage of COPD patients, with a correlation coefficient of 0.68. Our results indicated that occupational risk factor exposure levels were related to the severity of COPD significantly. The incubation period of COPD in the exposure group was significantly shorter than that in the non-exposure group. To prevent worked-related COPD, special attention and control efforts should be taken to reduce the level of occupational risk factors such as organic dust, irritating chemicals, etc in the work environments, especially in the industries of agriculture, forestry, animal husbandry and fishery, manufacturing, and mining.

This cross-sectional study evaluated the correlation between serum sodium levels (135-145 mmol/L) and biological aging in U.S. adults. Biological age, derived from multi-system biomarkers, provides a more accurate assessment of aging than chronological age. Hydration balance, reflected by serum sodium, may modulate age-related diseases and mortality, but its link to biological aging remains underexplored. Using NHANES data (1999-2018), we focused on normonatremic adults (≥20 years). The final cohort included 18,301 participants. Biological age was estimated using the Klemera and Doubal method, and ∆age (biological age-chronological age) was calculated. Associations were assessed using multivariate regression, generalized additive models, and threshold analysis. Subgroup analyses were conducted for variations across different populations. Nonlinear analysis revealed a U-shaped relationship between serum sodium and biological age. The lowest biological age occurred at 139.3 mmol/L: each 1 mmol/L increase below this threshold was associated with a reduction of 0.10 years in biological age (95% CI: -0.15, -0.05), whereas values above it showed a 0.08-year increase (95% CI: 0.04, 0.13). For ∆age, a negative association was observed below 141.2 mmol/L, with each increase linked to a 0.07-year decrease (95% CI: -0.10, -0.04). Subgroup analyses revealed significant interactions in diabetic and smoking populations. Maintaining serum sodium levels within an optimal range (138-142 mmol/L) may help delay biological aging. Hydration management may serve as a modifiable factor for healthy aging, particularly in high-risk groups such as individuals with diabetes or tobacco use.

Methods for the assessment of biological age - A systematic review.

In the process of safety culture construction in Chinese chemical industry, various interests and relationships of stakeholders involved are complicated, which hinders the process safety culture in chemical industry from being implemented practically. Thus, evolutionary game theory was used to draw the relationships between the stakeholders, including China chemical safety supervision department, chemical plants, and chemical plant workers. A system dynamics model was built to explore the dynamic relationships of process safety culture in Chinese chemical industry, and study the dynamic stability of stakeholders. The simulation results show that the strategy selections of China chemical safety supervision department, chemical plants, and chemical plant workers could reach a stable condition, which indicates that the evolutionary stable strategy exist in the current dynamic interaction among the three agents. Furthermore, a sensitivity analysis between state variables and several auxiliary variables were accomplished to reveal the internal relationships. The proposed new method of applying evolutionary game to process safety culture offers a solution to optimize safety culture construction.

During the Vietnam War, millions of liters of six tactical herbicides were sprayed on the southern Vietnam landscape to defoliate forests, to clear military perimeters and to destroy enemy food supplies. The environmental and human health impacts of spraying these herbicides, especially Agent Orange and those formulated with mixtures that included 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) which was contaminated with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) have been documented over the last 60 years. The dioxin TCDD clean-up efforts at former military bases and other Vietnam hotspots are ongoing. However, the lesser-told story was the environmental and human health impacts on the communities and chemical plant workers who manufactured Agent Orange and other herbicides that became contaminated with dioxin TCDD in the manufacturing processes at seven locations in the United States and one site in Canada. The pollution at these chemical plant sites, adjacent rivers and groundwater is well known within each affected state or province but not widely recognized beyond their localities. In this paper we assess the national long-term effects on land, groundwater and river resources where Agent Orange and other agricultural herbicides containing 2,4,5-T with unknown amounts of dioxin TCDD were manufactured, transported, and temporarily stored. The sites where residual tactical herbicides with contaminated by-products were applied to public lands or disposed of by military and civilian workers within the United States and Canada are identified. After 60 years, these communities are still paying the price for the U.S. Government, DOD and USDA decisions to provide and use agricultural herbicides as tactical chemical weapons during the Vietnam War (1962-1971). There have been human health issues associated with the chemical manufacture, transport, storage and disposal of these herbicides related to workers who moved these chemical weapons from United States and Canada to SE Asia. Most of these dioxin contaminated tactical herbicides were transported via railroads to ports at Mobile, Alabama and Gulfport, Mississippi. They were then loaded on ocean-going ships and transported via the Panama Canal for use during the Vietnam War. The objective of this study is to document the environmental and human consequences of the manufacture of tactical herbicides with dioxin TCDD and arsenic on the chemical plant, transportation, application, storage and disposal workers. The costs of cleanup of these North America chemical plant sites, transportation corridors, temporary and long-term storage areas, supply chain storage facilities with residual tactical herbicide, application, and disposal sites to date, is in the billions of dollars. Billions have been spent on hazardous waste incineration to destroy the dioxin TCDD or bury it in certified landfills. Government mandated environmental covenants are on titles of properties still contaminated with high levels of dioxin TCDD. If landowners attempt to rescind land use restrictions, many more billions of dollars will be needed to finish the environmental cleanup and restore natural resources. These cost estimates do not include the billions of dollars needed to treat the effects of dioxin TCDD exposure of U.S. and Canadian civilian workers who manufactured and handled these contaminated herbicides during the Vietnam War as well as address human health issues of their offspring.

A historical cohort study was conducted to evaluate the mortality experience of 6,831 employees of the Shell Oil Company, Deer Park, Texas, petroleum refinery and chemical plant with emphasis on cancer mortality. Subjects were all workers with potential plant exposure who were employed for at least 3 months during 1948-72. Vital status was determined as of 12/31/83 for 98% of the cohort and death certificates were obtained for 95.4% of 1,180 observed deaths. The statistical analyses excluded 159 female study members. For all causes of death combined, all cancers combined, and for most of the nonmalignant disease categories examined, there were deficits in mortality among refinery workers, chemical plant workers, and workers with experience in both areas. These deficits were generally most pronounced for chemical plant workers. An analysis of specific cancer sites revealed patterns of increased risk suggestive of a possible relationship between occupational exposures in the refinery and lympho-reticulosarcoma. Patterns of increased risk were also observed among chemical plant workers for a category of lymphopoietic tissue cancers, including multiple myeloma, myelofibrosis, polycythemia vera, and certain non-Hodgkin's lymphomas. Some very limited evidence of a possible workplace association was also found among refinery workers for leukemia and cancers of the central nervous system and biliary passages/liver. No evidence was found of an increased risk for cancer of the respiratory system or stomach or for malignant melanoma. A work history review of all suspect cancer excesses failed to identify any common work areas, job assignments, or exposure potentials, although the lack of detailed data on specific chemical exposures precluded accurate assessments of exposure-response.

Chronological age (CA) is the age given in years since birth whereas biological age (BA) is based on quantifiable changes on a cellular level measured through biomarkers. BA has a strong correlation with morbidity and mortality accounting for individual differences in the rate of aging and longevity. Since type 2 diabetes (T2D) is associated with increased morbidity and mortality, we hypothesized that BA would be increased in T2D diagnosed individuals and could be calculated with biomarkers from routine visits. In this study, we obtained deidentified data from three cohorts: (1) T2D (n= 686), (2) T1D (n= 540) (as a metabolic control) from Joslin Diabetes Center and (3) nondiabetics (n= 522) from the 2017-2018 National Health and Nutrition Examination Survey. Ages ranged from 20-80 years and for analysis, persons with diabetes were matched by age and gender to subjects without diabetes. Eight clinical biomarkers significantly correlated with CA in people without diabetes (p-values from 1.1 x10-98 to 5.6 x10-3). The Klemera and Doubal method (KDM) was used to calculate BA and results were confirmed using multiple linear regression. We observed a strong correlation between CA and BA in people without diabetes (R2 = 0.94, p&amp;lt; 0.0001) validating the biomarkers and KDM in our population. BA of people with T2D was, on average, 12 years higher than people without diabetes (p= 5.2 x10-187). BA of people with T1D was 15 years higher (p= 2.3 x10-236). The biomarkers with the strongest correlation to increased BA in T2D were systolic blood pressure (R2= 0.29, p&amp;lt; 2 x10-16) and A1c (R2= 0.27, p&amp;lt; 2 x10-16), suggesting that BA is dynamic and can be modified. Linear regression confirmed a significant increase of BA in persons with diabetes. In conclusion, increased BA in people with diabetes suggests accelerated aging, a critical concept for integrating the cellular understanding of aging with the environment and which can enhance future research on the relation between aging biology and diabetes. Disclosure N. Bahour: None. C. Aguayo-mazzucato: Consultant; Self; eGenesis. Funding Joslin Diabetes Center (to C.A-M.)

When aromatic compounds such as aminophenols1 and nitrobenzenes2 are absorbed they cause oxidation of the intracellular haemoglobin of circulating erythrocytes and sometimes induce severe meth aemoglobinaemia. We have also found that half oxidised haemoglobins are greatly increased in the erythrocytes of patients with hereditary meth aemoglobinaemia owing to a deficiency of NADH methaemoglobin reduc?ase.3 This prompted us to analyse the oxidised haemoglobins in circulating erythrocytes of workers in chemical plants. We found that half oxidised haemoglobins such as (a2+/?3+)2 and (oL3+?2+)2 were significantly increased in the erythro cytes of workers of some chemical factories of the Kansai area of Japan (A Tomoda et al, unpublished data). When analysing the haemoglobin patterns of workers from these factories by isoelectric focusing electrophoresis on polyacrylamide gel plates, we found that two unusual haemoglobins, which migrate to anodic positions on electrophoresis, were sig nificantly increased in the erythrocytes of all the workers studied in a chemical plant producing 4-chlor aminophenol. One of these haemoglobins moved to an anodic position consistent with that of haemoglobin X,4 and another moved to the position between haemoglobins X and A. The present report deals with cases with a pronounced increase in the concentrations of haemoglobins X and Y, half oxidised haemoglobins, and methaemoglobin in the eryth rocytes of workers in a chemical plant. Materials and methods

Response to Dr. Mitnitski's and Dr. Rockwood's Letter to the Editor: Biological Age Revisited

Atrial Fibrillation (AF) is associated with dementia and cognitive decline. AF is less prevalent among Blacks than Whites, although AF-related complications are more common in Blacks. In the general population, all-cause cognitive decline and dementia are more prevalent among Blacks than Whites. Thus, studying diverse populations with AF may advance our understanding of racial disparities in cognitive functioning. We created a measure of multisystem dysregulation (weathering), which includes but is more encompassing than aging, and examined its association with racial differences in cognition using data from the SAGE-AF study, a prospective cohort of >65-year olds with AF, at high stroke risk, and eligible for anticoagulation. Biological (as opposed to chronological) age among 974 participants was calculated using the Klemera and Doubal method using biomarkers representing physiological functioning, metabolism, and blood pressure. We defined weathering as the difference between biological and chronological age (weathering >0 indicates that biological age is higher than chronological age). We measured the association between weathering and the Montreal Cognitive Assessment (MoCA) score. Mean weathering (SD) was -0.7 (11.5) and 4.3 (12.6) for whites and non-whites, respectively. There was an interaction between race/ethnicity and weathering on cognition (P=0.004). In stratified analyses, higher weathering was associated with a lower MoCA score among both Whites and non-Whites but more so among non-whites (B = -0.09, 95% CI: -0.17, -0.02) for Whites (B = -0.03, 95% CI: -0.06, -0.01) for non-whites. Aging-related multisystem dysregulation is more strongly associated with worse cognition in non-whites than in whites.

We commend the overall evaluation by Cherrie et al. (2013) of the current occupational exposure limits (OELs) for respirable poorly-soluble low toxicity (PSLT) particles. As described in that paper, the epidemiological studies provide compelling evidence that exposure to PSLT at the current OELs has been associated with adverse health effects, including pulmonary fibrosis and lung function deficits. In contrast to Cherrie et al. (2013), we discuss here that the chronic inhalation studies in animals also provide evidence of the adverse pulmonary effects of PSLT.

Chronological age (CA) is determined by time of birth, whereas biological age (BA) is based on changes on a cellular level and strongly correlates with morbidity, mortality, and longevity. Type 2 diabetes (T2D) associates with increased morbidity and mortality; thus, we hypothesized that BA would be increased and calculated it from biomarkers collected at routine clinical visits. Deidentified data was obtained from three cohorts of patients (20–80 years old)—T2D, type 1 diabetes (T1D), and prediabetes—and compared to gender- and age-matched non-diabetics. Eight clinical biomarkers that correlated with CA in people without diabetes were used to calculate BA using the Klemera and Doubal method 1 (KDM1) and multiple linear regression (MLR). The phenotypic age (PhAge) formula was used with its predetermined biomarkers. BA of people with T2D was, on average, 12.02 years higher than people without diabetes (p < 0.0001), while BA in T1D was 16.32 years higher (p < 0.0001). Results were corroborated using MLR and PhAge. The biomarkers with the strongest correlation to increased BA in T2D using KDM were A1c (R2 = 0.23, p < 0.0001) and systolic blood pressure (R2 = 0.21, p < 0.0001). BMI had a positive correlation to BA in non-diabetes subjects but disappeared in those with diabetes. Mortality data using the ACCORD trial was used to validate our results and showed a significant correlation between higher BA and decreased survival. In conclusion, BA is increased in people with diabetes, irrespective of pathophysiology, and to a lesser extent in prediabetes.

Background and Objectives The accuracy of biological age (BA) calculations is highly influenced by the data used in each estimation. Expanding the data pool and efficiently integrating new data to refine the regression models for BA estimation are essential for reporting precise BA values. Current studies often rely on limited datasets, which can lead to less reliable BA predictions. Therefore, a tool capable of capturing new datasets dynamically is essential to ensure ongoing accuracy and robustness in BA estimation. Methods This study analysed a range of biomarkers, including systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, alanine aminotransferase, alkaline phosphatase, albumin, protein, urea and creatinine. SBP and DBP were used to calculate mean arterial pressure and pulse pressure. All biomarkers were standardised for consistent scaling across variables. Principal component analysis (PCA) was then employed to reduce dimensionality and highlight key components. BA was estimated using the Klemera and Doubal method. The BioDyn tool, developed using Python Flask, allows users to upload new datasets containing these biomarkers and seamlessly merge them with its existing data repository. This dynamic integration of new data enables automatic updates to regression models, continuously improving BA estimation accuracy. Additionally, BioDyn provides real-time visualisation of chronological age (CA) as a function of BA. Results The baseline dataset for this model consisted of data from 2,348 patients, which served as the initial training set. New data can be incorporated easily by uploading Excel files (Figure 1), allowing for seamless updates to the model as additional information becomes available. The relationship between CA and BA can be visualised dynamically (Figure 2). The distribution of the 12 variables used for model development is shown in Figure 1. The first principal component explained 17.56% of the total variance (Figure 3). Conclusions The BioDyn tool enables easy integration of new datasets through simple uploads, dynamically refining BA predictions and offering real-time visualisation of the relationship between CA and BA. This approach enhances the accuracy of the model and provides valuable insights into aging trends.Figure 1Figure 2

The mediating role of accelerated biological aging in the association between blood metals and cognitive function

The analytical review is devoted to the methodology for quantifying age-related changes, namely, the determination of biological age (BA). In contrast to the chronological age (CA), which is the same for all people born at the same time, BA can vary significantly and characterizes the rate of aging. Diagnostics of accelerated aging is of great clinical importance, as it allows predicting the development of age-related pathology. In addition, the BA calculation is used to assess various effects on the body, including geroprotectors. To calculate BA, a set of biomarkers of aging (BMA) is used. The most accurate method for determining BA is by measuring the methylation of certain genes (Horvath clock). However, this method is not available for clinical practice yet. Therefore, the development of BA models based on clinical BMS remains relevant. In addition, there is a need to assess the degree of age-related changes at the level of individual functional systems of the body (functional age). The list of BMA available for use in clinical practice is given in this review. The requirements are given that allow using the indicator of age-related changes as BMA. The main methods for calculating BV are multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), and neural network analysis. The criteria for assessing the quality of the BA model are described in this review. The MLR method, due to its simplicity, is most often used in clinical practice, however, it has a significant drawback, namely, the systematic error in calculating age, which is most pronounced in the extreme age groups. The article provides a method for correcting this error developed by the authors. The methodology of using MLR to obtain a formula for determining BA from a dataset BMA is described in detail. The theoretical foundations of the use of neural network algorithms for assessing the rate of aging are presented. The use of neural networks for assessing BA has shown their high efficiency by all criteria, in particular, the absence of a systematic error inherent in MLR-based methods. Keywords: biological age, biomarkers of aging, calculation methods.