Search Results (123)

Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual’s physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accelerated aging and increased cancer risk, including LN. Immunosenescence, the age-related decline in immune function characterized by thymic involution, altered lymphocyte populations, and chronic inflammation (inflammaging), appears to be a key mechanistic link between aging and LN development, potentially providing a more accurate predictor of cancer risk than mutation accumulation alone. Accelerated biological aging, measured by various clocks, correlates with LN risk and progression (e.g., in chronic lymphocytic leukemia), and may influence treatment tolerance and outcomes, particularly in older adults who are often burdened by frailty and comorbidities like sarcopenia. Integrating biological age assessments into clinical practice holds promise for refining diagnosis, prognosis, and personalizing treatment strategies (including guiding intensity and considering anti-aging interventions), and improving outcomes for patients with LN. This review synthesizes the current understanding of the intricate relationship between LN, immunosenescence, biological age, and aging clocks, highlighting clinical implications and key future research directions aimed at translating these insights into better patient care. Full article

Cystic fibrosis (CF) is the most common severe autosomal recessive disease among Caucasians. Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) mutated protein significantly improved the outcome of subjects with CF. In the present study, we studied epigenetic age, applying the Horvath clock model, in 52 adult subjects with CF, all treated with elexacaftor/tezacaftor/ivacaftor (ETI). At baseline (T0), we found that half of the subjects have a significantly accelerated epigenetic age and a worse lung function, evaluated by forced expiratory volume in one second (FEV1). One year of ETI therapy (T1) impacted both the parameters, indicating that therapy with modulators must be started early, particularly in CF subjects with impaired lung function. The second group of CF subjects had an epigenetic age lower than the chronological one at T0 and lung function was better maintained. In these subjects, ETI therapy further improved lung function and tended to increase the epigenetic age, possibly improving metabolic functions and the general state of well-being. This also translates into an increase in the physical activities of a group of subjects who, before the therapy, had grown up under a glass bell. The analysis of epigenetic age may represent a potential biomarker to assess the individual outcome of the therapy in subjects with CF, although long-term studies need to evaluate it. Full article

Background/Objectives: Digital technologies have become increasingly integrated into the daily lives of children and adolescents, largely because their interactive and visually engaging design is particularly suited to the younger users. The COVID-19 pandemic further accelerated this trend, significantly lowering the average age of access to the digital devices. However, scientific consensus remains divided regarding the developmental impact of digital media use—particularly its cognitive, motor, and emotional consequences—depending on whether the use is passive or active. This review aims to explore these effects across developmental stages, focusing on both behavioral and neurobiological dimensions, and to identify emerging risks and protective factors associated with digital engagement. Methods: A PRISMA review was conducted on the impact of digital media use among pre-school children and adolescents. Behavioral, psychosocial, and neurobiological aspects were examined, with specific attention to epigenetic changes, techno-stress, digital overstimulation, and immersive technologies (e.g., virtual and augmented reality). Results: The findings suggest that passive digital consumption is more often associated with negative outcomes, such as impaired attention and emotional regulation, especially in younger children. Active and guided use may offer cognitive benefits. Neurobiological research indicates that chronic exposure to digital stimuli may affect stress regulation and neural development, possibly via epigenetic mechanisms. Effects vary across developmental stages and individual vulnerabilities. Conclusions: A nuanced understanding of digital engagement is essential. While certain technologies can support development, excessive or unguided use may pose risks. This review provides age-specific recommendations to foster balanced and healthy technology use in children and adolescents. Full article

Blood bacterial DNA (BB-DNA) has been identified as a novel biomarker for metabolic dysfunction, yet its relationship with epigenetic features in type 2 diabetes mellitus (DM2) patients remains largely unexplored. This study investigated the relationship between BB-DNA and epigenetic, inflammatory, and aging-related markers in 285 elderly both with and without DM2. BB-DNA levels were higher in DM2 patients than in non-diabetic subjects, with the highest levels in those with severe renal impairment. BB-DNA showed a positive association with plasma IL-1β, linking bacterial DNA to systemic inflammation. Epigenetic analysis revealed a negative correlation between BB-DNA and DNA methylation-based leukocyte telomere length, suggesting accelerated aging in DM2. Additionally, BB-DNA was positively associated with DNAm-based biological age estimators, particularly DNAmPhenoAge and DNAmAge Skin Blood Clock. BB-DNA also correlated with DNAmVEGFA and DNAmCystatin C, key markers of diabetic nephropathy and vascular dysfunction. Furthermore, BB-DNA levels were associated with hypomethylation of genes involved in inflammation (e.g., IL1β, TNFα, IFNγ), cellular senescence (p16, p21, TP53), and metabolic regulation (e.g., IGF1, SREBF1, ABCG1, PDK4). These associations suggest that increased BB-DNA may reflect and potentially promote a pro-inflammatory and pro-senescent epigenetic profile in DM2. Importantly, many of these associations remained significant after adjusting for diabetes status, supporting BB-DNA as a robust biomarker across clinical subgroups. These findings provide new insights into the relationship between BB-DNA, inflammation, and epigenetic aging in DM2, highlighting BB-DNA as a potential biomarker for disease progression and complications, particularly in relation to renal dysfunction and systemic inflammation. Full article

Plant polyphenols have emerged as potent bioactive molecules that can modulate key cellular pathways associated with aging and chronic disorders. The Mediterranean diet and the traditional Japanese style of life are rich in polyphenol-containing foods and beverages, and epidemiological evidence links these dietary patterns to increased longevity and reduced morbidity. This narrative review examines the chemical description of plant polyphenols, their mechanisms of action, including anti-inflammatory, antioxidant, and hormetic effects, and how supplementation or a diet rich in these compounds may provide further life extension. We discuss the major classes of polyphenols present in the Mediterranean dietary pattern (e.g., resveratrol and hydroxytyrosol) and in the Japanese diet (e.g., epigallocatechin gallate and soy isoflavones), comparing their biological behaviors and cooperative effects on metabolic, cardiovascular, and neurodegenerative conditions. We also examine a few preclinical and clinical studies that explain the beneficial impact of these chemicals on aging-associated biomarkers. Furthermore, both dietary habits are characterized by low consumption of processed foods and sugary carbonated drinks and reduced utilization of deep-frying with linoleic acid-rich oils, a practice that reduces the formation of harmful lipid peroxidation products, notably 4-hydroxynonenal, known to be implicated in accelerating the aging process. The Mediterranean dietary pattern is also characterized by a low/moderate daily consumption of wine, mainly red wine. This work debates emerging evidence addressing issues of bioavailability, dosage optimization, and formulation technologies for polyphenol supplementation, also comparing differences and similarities with the vegan and vegetarian diets. We also explore how these chemicals could modulate epigenetic modifications that affect gene expression patterns pertinent to health and aging. In conclusion, we aim to show a consolidated framework for the comprehension of how plant polyphenols could be utilized in nutritional strategies for potentiating life expectancy while stimulating further research on nutraceutical development. Full article

Youth exposed to early-life adversity (ELA) are at greater risk for poorer physical and mental health outcomes in adolescence and adulthood. Although the biological mechanisms underlying these associations remain elusive, DNA methylation (DNAm) has emerged as a potential pathway. DNAm-based measures of epigenetic age have been associated with ELA, indicating accelerated aging. According to the stress sensitization hypothesis, prenatal adversity may further heighten sensitivity to subsequent stressors in childhood and adolescence. This study examined the associations between ELA and six epigenetic aging measures, considering both the timing of adversity and the participant’s sex. Data were drawn from the Quebec Longitudinal Study of Child Development, with two cumulative indices of ELA derived from prospectively collected data: the Perinatal Adversity and the Child and Adolescent Adversity indices. Higher Perinatal Adversity scores were associated with accelerated DunedinPACE scores. No significant associations were found between ELA and the other epigenetic clocks, nor did we find support for the stress sensitization hypothesis—though a sex-specific trend emerged among girls. The findings suggest that DunedinPACE may be more sensitive to variations in ELA than other clocks. Future research should systematically investigate sex-dimorphic associations between ELA and epigenetic aging, with particular attention to the impact of perinatal adversity. Full article

Background: To date, there are no precise clinical and laboratory methods to accurately predict the onset of fertility decline in women, with chronological age being the ultimate predictor. This has led to increased interest in developing methods to determine biological age, as it provides a more accurate understanding of individual age-related physiological changes. Methods: In this study, we developed a model for estimating biological age based on DNA methylation levels in the ELOVL2, TRIM59, C1orf132, FHL2, and KLF14 genes using pyrosequencing. The model was tested in 64 Russian women, aged 25–39 years, to find an association between epigenetic age, infertility, low anti-Müllerian hormone (AMH) levels, and assisted reproductive technology (ART) failure. Results: The predictive performance of the model was evaluated. The mean absolute deviation of the model was 2.8 years; the mean absolute error was 2.6 years (R² = 0.95). In the studied cohort, 33% of women exhibited epigenetic age acceleration (EAA), while 45% showed epigenetic age deceleration (EAD). All women with an EAA of ≥3 years (n = 6) had a history of infertility. Conclusions: In this study, no statistically significant associations were observed between EAA/EAD and AMH, body mass index, infertility, or ART failure in women. Full article

Electrical stimulation (ES) is widely employed in both clinical therapies and research settings where it has shown promise in promoting tissue regeneration, wound healing, and inflammation control. Research has also highlighted ES as a regulator of DNA demethylation, which plays a critical role in nerve regeneration and cellular repair mechanisms. While the impact of ES on epigenetic processes is recognized, its broader effects on cellular functions, particularly in inflammation and wound healing, are less understood. We recently showed how ES impacts inflammatory states by modulating transcriptomic and metabolomic profiles in a 3Din vitromodel where human fibroblasts and keratinocytes are included in a collagen matrix, i.e., even in the absence of the nervous system. Here, we propose to deepen our exploration on the differential effects on DNA methylation, including an investigation of the correlation with age acceleration using a mitotic clock. These results confirm and caution on the differential effect of DC on inflamed and non-inflamed samples and suggest an involvement of direct current stimuli at 1 V ($DC1$) in the control of senescent processes associated with mitosis and inflammation; the mechanistic details of these will have to be clarified with additional experiments. Full article

Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by both global hypomethylation and focal hypermethylation, contribute to the emergence of cancer. We discuss mechanisms of DNA methylation drift, the development of epigenetic clocks, and the role of entropy and epigenetic mosaicism, in aging and tumorigenesis. Emphasis is placed on how stochastic methylation errors accumulate in aging cells and lead to epiallelic shifts and gene silencing, predisposing tissues to malignant transformation, even despite recently increased cancer incidences at younger ages. We also highlight the translational potential of DNA methylation-based biomarkers, and therapeutic targets, in age-related diseases. By framing cancer as a disease of accelerated epigenetic aging, this review offers a unifying perspective and calls for age-aware approaches to both basic research and clinical oncology. Full article

Nowadays, scientists are making efforts to elucidate the mechanisms involved in the phenotypic changes underlying the aging process in order to develop favorable therapeutical interventions. Epigenetic modifications, in particular DNA methylation, play a crucial role in the aging process, and this parameter has been used to set epigenetic clocks, algorithms that predict an individual’s biological age based on a defined set of CpGs. In this review, we focus on the most recent literature to discuss the use of epigenetic clocks in the context of cognitive decline and dysregulation of Alzheimer’s disease (AD)-related gene expression. We have summarized all published scientific papers in which epigenetic clocks have been applied to measure age acceleration in blood and brain specimens from patients affected with AD. Progressive age acceleration, consistent with a specific DNA methylation signature, was observed in patients affected by AD, and it was correlated with the onset of complex diseases, mitochondrial alterations, dementia and cognitive decline, even in the early stages of these conditions. The use of epigenetic clocks might be a valuable biomarker to enable an earlier identification of ideal measures to reverse modifications caused by aging and to mitigate multiple aspects of disease/aging mechanisms. Full article

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article

Aging affects all tissues in an organism, including the tracheobronchial tree, with structural and functional changes driven by mechanisms such as oxidative stress, cellular senescence, epigenetic modifications, mitochondrial dysfunction, and telomere shortening. Airway aging can be accelerated by intrinsic or extrinsic factors. This review brings together information from the literature on the molecular changes occurring in all layers of the tracheobronchial airway wall. It examines the biomolecular changes associated with aging in the mucosa, submucosa, cartilage, and smooth muscle of the airways. At the mucosal level, aging reduces ciliary function and disrupts mucin homeostasis, impairing mucociliary clearance and contributing to chronic respiratory diseases such as COPD (Chronic Obstructive Pulmonary Disease). Cellular senescence and oxidative stress drive extracellular matrix remodeling and chronic inflammation. Airway cartilage undergoes age-related changes in collagen and fibronectin composition, leading to increased stiffness, while heightened MMP (Matrix Metalloproteinases) activity exacerbates ECM (extracellular matrix) degradation. In airway smooth muscle, aging induces changes in calcium signaling, hypertrophy, and the secretion of pro-inflammatory mediators, further perpetuating airway remodeling. These changes impair respiratory function and increase susceptibility to chronic respiratory conditions in the elderly. By consolidating current knowledge, this review aims to provide a comprehensive overview of the molecular changes occurring in the respiratory tract with aging and to highlight new molecular perspectives for future research on this topic. Full article

Our study tests residential segregation as an explanation for biological aging disparities between Black and White Americans. We analyze data from 288 Black and White older-age adults who participated in Wave 6 (2019) of the Americans’ Changing Lives study, a nationally representative cohort of adults in the contiguous United States. Our outcome of interest is epigenetic age acceleration assessed via five epigenetic clocks: GrimAge, PhenoAge, SkinBloodAge, HannumAge, and HorvathAge. Residential segregation is operationalized at the census tract level using the Getis-Ord G_i* statistic and multilevel modeling procedures that adjust for state-level clustering. We uncover three key findings. First, epigenetic age profiles are comparable among White respondents regardless of where they live. Second, Black respondents express roughly three years of accelerated epigenetic age (GrimAge), relative to White counterparts, regardless of where they live. Third, diminished education levels and homeownership rates, coupled with elevated levels of traumatic stress and smoking, explain why Black residents in segregated Black areas exhibit accelerated epigenetic age. However, these factors do not explain why Black respondents living outside segregated Black areas also exhibit epigenetic age acceleration. Our findings suggest residential segregation only partially explains why Black Americans tend to live shorter lives than White Americans. Full article

Background: Psychosis is one of the leading causes of disability worldwide. Individuals with early-onset psychosis (EOP) tend to experience a worse prognosis and shorter life expectancy. The etiology of EOP remains unclear, but epigenetic mechanisms are known to serve as the interface between environmental exposures and biological processes to better understand its etiology. Objectives: We characterized the sociodemographic and clinical characteristics, as well as genome-wide epigenetic markers, in Mexican patients with EOP. Methods: We estimated epigenetic age, performed an epigenome-wide association study, and finally developed an epigenetic risk score (MRS) to predict manifestations of psychosis. Results: We found that patients with EOP have a higher epigenetic age using Wu’s clock (p = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, p = 0.046), global functioning (Wu’s clock, p = 0.027), and psychiatric admissions (DNAmTL, p = 0.038). In addition, we observed that a reduction in years of schooling is associated with an increase on epigenetic age (Levine’s clock, β = 5.07, p = 0.001). In our epigenome-wide association study, we identified eight CpGs associated with EOP. Noteworthy, a psychosis-methylation risk score (EOP-MRS) was associated with panic disorder (β = 1.36, p = 0.03), as well as auditory (β = 1.28, p = 0.04) and visual (β = 1.22, p = 0.04) hallucinations. Conclusions: Years of education have an impact on epigenetic age. Additionally, our study suggests associations of DNA methylation with EOP. Finally, we developed an MRS that associates clinical manifestations of psychosis. Full article

Ageing is influenced by a complex interplay of genetic, environmental, and lifestyle factors, with increasing evidence highlighting the exposome as a key determinant of healthspan. This review explores the impact of environmental exposures, focusing in particular on pollution, endocrine disruptors, and climate change on the development of age-related diseases such as cardiovascular diseases (CVDs), cancer, and metabolic disorders. Additionally, it examines protective factors that contribute to healthy ageing. A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar, focusing on studies published between 2000 and 2025. Findings indicate that chronic exposure to pollutants accelerates cellular ageing through mechanisms such as oxidative stress, inflammation, and epigenetic dysregulation. In contrast, longevity hotspots—Blue Zones, Cilento and the mountain villages of Sicily (Sicani and Madonie Mountains)—illustrate how traditional dietary patterns, strong social structures, and reduced environmental toxicity contribute to exceptional health and longevity. Mechanistically, exposome-driven alterations in immune-inflammatory pathways and epigenetic regulation play a central role in modulating ageing trajectories. Understanding these interactions is essential for developing targeted strategies to mitigate harmful exposures and enhance protective factors. This review underscores the urgent need for integrative public health policies that address the environmental determinants of ageing, ultimately promoting a longer and healthier lifespan. Full article