The Fifth Annual Symposium of the Midwest Aging Consortium.

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28-30, 2024, was hosted by The Ohio State University in Columbus, Ohio and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms.

Sex-related DNA methylation is associated with inflammation and gene expression in the lungs of healthy individuals.

Lung cancer exhibits sex-biased molecular characteristics and epidemiological trends, suggesting a need for sex-specific approaches to understanding its etiology and treatment. DNA methylation alterations play critical roles in lung carcinogenesis and may serve as valuable biomarkers for precision medicine strategies. We employed the Infinium MethylationEPIC array to identify autosomal sex-related differentially methylated CpG sites (DM-CpGs) in lung epithelium of healthy individuals (32 females and 37 males) while controlling for age, BMI, and tobacco use.

A scoping review of the toxicity and health impact of IQOS.

This work aims to summarize the current evidence on the toxicity and health impact of IQOS, taking into consideration the data source. On 1 June 2022, we searched PubMed, Web of Science, and Scopus databases using the terms: 'heated tobacco product', 'heat-not-burn', 'IQOS', and 'tobacco heating system'. The search was time-restricted to update a previous search conducted on 8 November 2021, on IQOS data from 2010-2021.

Accelerated epigenetic age, inflammation, and gene expression in lung: comparisons of smokers and vapers with non-smokers.

Background: Cigarette smoking and aging are the main risk factors for pulmonary diseases, including cancer. Epigenetic aging may explain the relationship between smoking, electronic cigarette vaping, and pulmonary health. No study has examined smoking and vaping-related epigenetic aging in relation to lung biomarkers.

Sex-specific lung inflammation and mitochondrial damage in a model of electronic cigarette exposure in asthma.

The prevalence of electronic cigarette (EC) use among adult with asthma has continued to increase over time, in part due to the belief of being less harmful than smoking. However, the extent of their toxicity and the involved mechanisms contributing to the deleterious impact of EC exposure on patients with preexisting asthma have not been delineated. In the present project, we tested the hypothesis that EC use contributes to respiratory damage and worsening inflammation in the lungs of patients with asthma.

Untargeted Metabolomics and Body Mass in Adolescents: A Cross-Sectional and Longitudinal Analysis.

Obesity in children and adolescents has increased globally. Increased body mass index (BMI) during adolescence carries significant long-term adverse health outcomes, including chronic diseases such as cardiovascular disease, stroke, diabetes, and cancer. Little is known about the metabolic consequences of changes in BMI in adolescents outside of typical clinical parameters.

Long-Term Impact of Daily E-cigarette Exposure on the Lungs of Asthmatic Mice.

Introduction: Although the greater popularity of electronic cigarettes (EC) among asthmatics is alarming, there is limited knowledge of the long-term consequences of EC exposure in asthmatics.

Aims And Methods: Mild asthmatic C57/BL6J adult male and female mice were established by intranasal insufflation with three combined allergens. The asthmatic and age and sex-matched' naïve mice were exposed to air, nicotine-free (propylene glycol [PG]/vegetable glycerin [VG]-only), or PG/VG+Nicotine, 4 hours daily for 3 months.

Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

Background: Mitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use.

Methods: Bronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression.

Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking.

Unlabelled: The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes.

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study.

Background: Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA).

Methods: Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60-65.

Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes.

Obesity, diabetes, and hypertension have increased by epidemic proportions in recent years among African Americans in comparison to Whites resulting in significant adverse cardiovascular disease (CVD) disparities. Today, African Americans are 30% more likely to die of heart disease than Whites and twice as likely to have a stroke. The causes of these disparities are not yet well-understood.

SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells.

Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, and cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxia, cytotoxicity, and inflammatory insults to renal tubular epithelial cells (RTECs), resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI.

Inflammasome Adaptor ASC Is Highly Elevated in Lung Over Plasma and Relates to Inflammation and Lung Diffusion in the Absence of Speck Formation.

Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymers in lung bronchoalveolar lavage fluid (BALF) might serve as a marker of lung inflammasome activity.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

Background: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.

Methods: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015.

Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group.

FoxO1 is a critical regulator of M2-like macrophage activation in allergic asthma.

Background: The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment.

Methylation of imprinted IGF2 regions is associated with total, visceral, and hepatic adiposity in postmenopausal women.

Excess body fat, especially intra-abdominal fat, is a leading risk factor for metabolic diseases. Differentially methylated regions (DMRs) of two imprinted genes, insulin-like growth factor 2 (IGF2) and H19, have been associated with obesity due to their important roles in regulating body composition, but have not been examined in relation to intra-abdominal fat depots. Total body fat from whole-body dual energy X-ray absorptiometry and visceral and liver fat contents from abdominal magnetic resonance imaging in 48 healthy women aged 60-65 years (of White or Japanese ancestry) were each regressed on circulating leukocyte DNA methylation levels of IGF2 (at DMR0, DMR2a, and DMR2b) and H19 (at CTCF3) as assessed by pyrosequencing, while adjusting for age and race/ethnicity.

DNA Methylation as a Biomarker of Aging in Epidemiologic Studies.

Cancer is largely an aging disease. Accelerated biological aging may be the strongest predictor of cancer and other chronic disease risks. In the absence of reliable and quantifiable biomarkers of aging to date, it has long been observed that tumorigenesis shares distinct epigenetic alterations with the aging process.

Landscape of genome-wide age-related DNA methylation in breast tissue.

Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology.