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.

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.

Sarcopenia, a musculoskeletal disease characterized by the progressive loss of skeletal muscle mass, strength, and physical performance, presents significant challenges to global public health due to its adverse effects on mobility, morbidity, mortality, and healthcare costs. This comprehensive review explores the intricate connections between sarcopenia and low birth weight (LBW), emphasizing the developmental origins of health and disease (DOHaD) hypothesis, inflammatory processes (inflammaging), mitochondrial dysfunction, circadian rhythm disruptions, epigenetic mechanisms, and genetic variations revealed through genome‐wide studies (GWAS). A systematic search strategy was developed using PubMed to identify relevant English‐language publications on sarcopenia, LBW, DOHaD, inflammaging, mitochondrial dysfunction, circadian disruption, epigenetic mechanisms, and GWAS. The publications consist of 46.2% reviews, 21.2% cohort studies, 4.8% systematic reviews, 1.9% cross‐sectional studies, 13.4% animal studies, 4.8% genome‐wide studies, 5.8% epigenome‐wide studies, and 1.9% book chapters. The review identified key factors contributing to sarcopenia development, including the DOHaD hypothesis, LBW impact on muscle mass, inflammaging, mitochondrial dysfunction, the influence of clock genes, the role of epigenetic mechanisms, and genetic variations revealed through GWAS. The DOHaD theory suggests that LBW induces epigenetic alterations during foetal development, impacting long‐term health outcomes, including the early onset of sarcopenia. LBW correlates with reduced muscle mass, grip strength, and lean body mass in adulthood, increasing the risk of sarcopenia. Chronic inflammation (inflammaging) and mitochondrial dysfunction contribute to sarcopenia, with LBW linked to increased oxidative stress and dysfunction. Disrupted circadian rhythms, regulated by genes such as BMAL1 and CLOCK, are associated with both LBW and sarcopenia, impacting lipid metabolism, muscle mass, and the ageing process. Early‐life exposures, including LBW, induce epigenetic modifications like DNA methylation (DNAm) and histone changes, playing a pivotal role in sarcopenia development. Genome‐wide studies have identified candidate genes and variants associated with lean body mass, muscle weakness, and sarcopenia, providing insights into genetic factors contributing to the disorder. LBW emerges as a potential early predictor of sarcopenia development, reflecting the impact of intrauterine exposures on long‐term health outcomes. Understanding the complex interplay between LBW with inflammaging, mitochondrial dysfunction, circadian disruption, and epigenetic factors is essential for elucidating the pathogenesis of sarcopenia and developing targeted interventions. Future research on GWAS and the underlying mechanisms of LBW‐associated sarcopenia is warranted to inform preventive strategies and improve public health outcomes.

DNA methylation represents a crucial epigenetic mechanism orchestrating gene expression, cellular homeostasis, and the aging trajectory. Dysregulation of DNA methyltransferases (DNMTs)-the enzymes catalyzing this process-has been implicated in a wide spectrum of chronic conditions, including cancer, cardiovascular and metabolic disorders, and neurodegenerative diseases. Emerging evidence suggests that food-derived bioactive compounds can act as DNMT inhibitors, reshaping epigenetic landscapes. This systematic review, registered in PROSPERO (CRD42022320316), critically evaluated in vitro, in vivo animal, and ex vivo studies investigating the effects of dietary bioactives on DNMT expression and activity. A thorough search of PubMed up to 23 May, 2025, yielded 103 studies, of which 76 met the inclusion criteria. Eligible publications were original, peer-reviewed, and provided evidence from in vitro, in vivo animal, or ex vivo models. Frequently studied bioactives included epigallocatechin-3-gallate, curcumin, genistein, resveratrol, sulforaphane, and folate. Notably, nearly 90% of studies reported DNMT inhibition-often dose- and time-dependent. Approximately 21% defined minimal effective concentrations, predominantly for isolated compounds. Several studies described synergistic interactions between bioactives, and emerging data highlighted the gut microbiota's mediating role in epigenetic modulation. Despite promising outcomes, the predominance of preclinical evidence and variability in experimental protocols and dosing limit the immediate translational impact. Nonetheless, current findings underscore the promise of dietary DNMT modulators as foundational elements for precision nutrition strategies aimed at promoting healthy aging and mitigating age-associated disease risk. The potential application of DNA methylation age as a biomarker of biological aging has been increasingly supported by recent literature, reinforcing its relevance in future nutritional epigenetics research. Further well-designed clinical trials are warranted to assess long-term efficacy, safety, and bioavailability of these compounds and to validate their use in personalized epigenetic interventions using biological aging markers. This review was funded by the European Union-Next Generation EU, PNRR Project Age-It (DM 1557 11.10.2022), and the University of Padua SID Grant (2024DCTV1SIDPROGETTI-00194).

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NCs), and induced sputum (IS) one year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February–May 2020), compared to COPD patients, model for “aged lung”. Data from questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p < 0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p < 0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p ≤ 0.05) and NCs (p < 0.001) and were biologically older than COPD patients (p < 0.05). These findings suggest the need to monitor aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

As human life expectancy continues to rise, ageing and age-related diseases have become critical societal challenges, driving extensive research across genetics, molecular biology, biochemistry, and behavioral sciences. In this context, domestic dogs (Canis lupus familiaris) offer a unique model for ageing research due to their shared environmental exposures with humans, diverse genetic profiles, and relatively short lifespans. This review aims to identify potential biomarkers of ageing in dogs, facilitating a deeper understanding of age-related mechanisms and supporting the evaluation of interventions designed to promote healthy ageing. We present a research of peer-reviewed literature on age-related variations of various parameters across multiple biological systems, including epigenetic, telomere, immune, metabolic, and cognitive markers in dogs. Our findings highlight several robust biomarkers, such as DNA methylation-based epigenetic clocks, telomere attrition, CD4+/CD8+ T-cell ratio, hematological markers (e.g., globulin levels), and cognitive function scores. These biomarkers demonstrate strong parallels with human ageing processes, particularly concerning genomic and epigenetic alterations. However, challenges remain, including breed-specific variability, body size differences, and inconsistent evidence regarding inflammageing markers, such as pro-inflammatory cytokines. Despite these limitations, indicators of chronic inflammation (e.g., anemia of chronic disease and elevated globulins) are evident in older dogs. Future research directions include the standardization of biomarker protocols for dogs, the development of longitudinal studies to track dynamic age-related changes, and further exploration of emerging biomarkers, such as those related to microbiome composition and oxidative stress.