Background: Further knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE–DNA) adducts.Methods: The study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE–DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships.Results: Anti-B[a]PDE–DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE–DNA (p = 0.028 andp = 0.018), particularly in males (p = 0.006 andp = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE–DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003).Conclusion: New findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases.Capsule: Everyday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.

Background: Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn). Methods: The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup_PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ_PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)–DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA_changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships. Results: In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA_changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup_PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA_changes (p < 0.0001) which is in turn triggered by Occup_PAHs and Environ_PAHs. Conclusions: Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented.

Astronauts returning from space missions often exhibit health issues mirroring age-related conditions, suggesting spaceflight as a potential driver of biological ageing and age-related diseases. To unravel the underlying mechanisms of these conditions, this comprehensive review explores the impact of the space "exposome" on the twelve hallmarks of ageing. Through a meticulous analysis encompassing both space environments and terrestrial analogs, we aim to decipher how different conditions influence ageing hallmarks. Utilizing PubMed, we identified 189 studies and 60 meet screening criteria. Research on biological ageing in space has focused on genomic instability, chronic inflammation, and deregulated nutrient sensing. Spaceflight consistently induces genomic instability, linked to prolonged exposure to ionizing radiation, triggers pro-inflammatory and immune alterations, resembling conditions in isolated simulations. Nutrient sensing pathways reveal increased systemic insulin-like growth-factor- 1. Microbiome studies indicate imbalances favoring opportunistic species during spaceflight. Telomere dynamics present intriguing patterns, with lengthening during missions and rapid shortening upon return. Despite a pro-ageing trend, some protective mechanisms emerge. Countermeasures, encompassing dietary adjustments, prebiotics, postbiotics, symbiotics, tailored exercises, meditation, and anti-inflammatory supplements, exhibit potential. Spaceflight's impact on ageing is intricate, with diverse findings challenging established beliefs. Multidisciplinary studies provide guidance for future research in this field.

Background: Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells’ activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation.Purpose of the study: The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation.Material and Methods: A systematic review of several databases has been conducted. The Newcastle–Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively.Results: Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia–reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies.Conclusions: Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.

Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p = 0.0143) and increased Disease Count Index (OR = 0.6912; p = 0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.

Aging is driven by fundamental mechanisms like oxidative stress, telomere shortening and changes in DNA methylation, which together prepare the ground for age-related diseases. Botanical extracts, rich in bioactive phytoconstituents, represent a promising resource for developing therapies that target these mechanisms to promote healthy aging. This study explores the geroprotective potential of Monarda didyma L. extract. In vitro analyses revealed the extract’s strong antioxidant activity, ability to reduce telomere shortening, and capacity to protect against DNA damage, thereby decreasing cellular senescence and improving endothelial function. The randomized, double-blind clinical trial demonstrated that daily oral supplementation with the extract significantly improved leukocyte telomere length (LTL) and stabilized DNA methylation age (DNAmAge) in the intervention group, while the placebo group experienced accelerated epigenetic aging and hypermethylation of critical age-related genes (ELOVL2 and FHL2). The intervention group also reported enhanced quality of life, particularly in the physical domain, along with improved movement and quality sleep indices detected by questionnaire and wearable sensors. These compelling findings position Monarda didyma L. extract as a powerful candidate for future geroprotective therapies, with the potential to significantly impact healthy aging.