Relationship between telomere length, genetic traits and environmental/occupational exposures in bladder cancer risk by structural equation modelling

Background: Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects (p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention

Dually Cross-Linked Core-Shell Structure Nanohydrogel with Redox–Responsive Degradability for Intracellular Delivery

A redox-responsive nanocarrier is a promising strategy for the intracellular drug release because it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation conditions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electronmicroscopy, and further confirmed by Fourier transforminfrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via theMichael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell structure nanohydrogel can be considered a promising tool for the potential intracellular delivery of different pharmaceutical applications, including for cancer therapy

Mitigating cellular aging and enhancing cognitive functionality: visual arts-mediated Cognitive Activation Therapy in neurocognitive disorders

The growing phenomenon of population aging is redefining demographic dynamics, intensifying age-related conditions, especially dementia, projected to triple by 2050 with an enormous global economic burden. This study investigates visual arts-mediated Cognitive Activation Therapy (CAT) as a non-pharmacological CAT intervention targets both biological aging [leukocyte telomere length (LTL), DNA methylation age (DNAmAge)] and cognitive functionality. Aligning with a broader trend of integrating non-pharmacological approaches into dementia care. The longitudinal study involved 20 patients with mild to moderate neurocognitive disorders. Cognitive and functional assessments, and biological aging markers -i.e., LTL and DNAmAge- were analyzed before and after CAT intervention. Change in LTL was positively correlated with days of treatment (p =0.0518). LTL significantly elongated after intervention (p =0.0269), especially in men (p =0.0142), correlating with younger age (p =0.0357), and higher education (p =0.0008). DNAmAge remained instead stable post-treatment. Cognitive and functional improvements were observed for Copy of complex geometric figure, Progressive Silhouettes, Position Discrimination, Communication Activities of Daily Living—Second edition, Direct Functional Status (p < 0.0001) and Object decision (p =0.0594), but no correlations were found between LTL and cognitive gains. Visual arts-mediated CAT effectively mitigates cellular aging, especially in men, by elongating LTL. These findings underscore the potential of non-pharmacological interventions in enhancing cognitive and functional status and general well-being in dementia care. Further research with larger and longer-term studies is essential for validation

The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators

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

A “glympse” into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin‐4 for the assessment of glymphatic system in Alzheimer's disease and other dementias

The glymphatic system (GS) is a whole‐brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non‐invasive methods based on magnetic resonance imaging (MRI) along with aquaporin‐4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi‐shell diffusion‐weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF‐AQP4. CSF‐AQP4 levels and MRI measures—including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW‐WM) and mean kurtosis (MK‐WM), diffusion tensor imaging analysis along the perivascular spaces (DTI‐ALPS) (mean, left and right)—were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF‐AQP4 (exp(b) = 2.05, p = .005) and FW‐WM FW‐WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF‐AQP4 and FW‐WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK‐WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF‐AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Exploring mechanisms of biological aging in susceptible subjects

The aim of the PhD project is to explore molecular mechanisms that characterize the process of biological aging with the main focus on the two most prominent early hallmarks of biological aging such as telomere length (TL) and epigenetic age, also defined as DNA methylation age (DNAmAge), in order to answer the following main questions: 1) If environmental and occupational exposures accelerate the biological aging in healthy subjects and in subjects affected by age-relate disease. 2) If, on the other hand, correct lifestyle including an intensive meditation/relaxing training in healthy subjects and patients with cardiovascular diseases, and heart transplantation in patients suffering from end-stage heart failure, slow down biological aging. To this aims we analyzed biological aging indicators in easily available human tissue (blood leucocytes) and in target organ (i.e., heart of donors and recipients and lung from induced sputum of Chronic Obstructive Pulmonary Disease (COPD) patients). Study populations consist of: 1) HEALTHY SUBJECTS EXPOSED TO GERONTOGENIC ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES a) 71 night-shift workers and 84 day workers as control exposed to circadian rhythm disruption. b) 585 individuals from general population living in North-East Italy exposed to everyday exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution. c) A prospective cohort study of women and men aged 70 years and older from the area of Treviso, which is characterized by the highest longevity in Italy. TRELONG longitudinal study population comprises 576 subjects at baseline, 300 and 200 subjects at T1 and T2 respectively, exposed to lifestyle and occupational exposures. 2) SUBJECTS AFFECTED BY AGE-RELATE DISEASES a) Bladder cancer (BC), a chronic disease characterized by the interaction between environmental/occupational and genetic risk factors. Study population includes newly diagnosed, histologically confirmed BC patients, admitted to the Urology Departments of two large hospitals from 1997 to 2000. Controls are 94 non-neoplastic urological patients matched to cases by age, period and hospital of admission. b) Idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD) as the most common manifestations of aging-mediated diseases. Study population consists of n=101 IPF patients (ATS/ERS/JRS/ALAT guidelines) and n=18 moderate COPD patients (GOLD 2019) all enrolled at the ambulatory of Pneumology and Respiratory Physiopathology Wards – Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova. 3) HEALTHY SUBJECTS AND PATIENTS EXPOSED TO REJUVENATING FACTORS a) Patients after myocardial infarction (n=20) and healthy control individuals (n=10), age- and gender-matched, trained to meditation and relax for 60 days. b) 17 recipients receiving the heart from 17 donors in the period February 2018 - February 2019. The local Ethics Committee - University of Padova, approved the study protocols (3843/AO/16 and 3054/AO/14). Main finding stemming from our results revels that: 1) HEALTHY SUBJECTS EXPOSED TO GERONTOGENIC ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES - Night-shift work is associated with increased systemic inflammation as proved by higher C-reactive protein (CRP) levels among night shift workers. LTL is reduced by CRP, while is positively associated with long pentraxin 3 (PTX3) that, by orchestrating an efficient governance of inflammatory processes, may protect telomere from attrition. This would make nocturnal workers more susceptible to premature LTL shortening and aging. - Certain preventable everyday life exposures to PAHs diminish LTL and even LmtDNAcn, in particular in males, acting through anti-B[a]PDE–DNA adduct formation. Our findings show that indoor activities and diet represent the primary determinants of PAHs exposure in increasing anti-B[a]PDE–DNA adduct levels that in turn decrease in presence of detoxifying GSTM1. - In TRELONG population LTL significantly declines over the years, from baseline to follow up, also considering only n=161 subjects whit all measurements at three different time points. 2) SUBJECTS AFFECTED BY AGE-RELATE DISEASES - LTL attrition is a critical event in BC. In particular, BC risk is increased directly by LTL attrition that depends on some preventable everyday life exposures genetically modulated. Furthermore, indirect effects on BC risk are evidenced via LTL reduction through age and genetic polymorphisms involved in modulating response to environmental exposure. - IPF patients in follow up present an increase in LTL positively related to the duration of antifibrotic treatment, with both pirfenidone and nintedanib, and with a decrease in lung function decline. These results would suggest that telomere shortening in IPF patients treated with antifibrotic drugs may be reversed leading to an increase in LTL. - In COPD patients: a) lung, i.e., pulmonary cells obtained from induced sputum, is biologically older than blood, as determined by TL and DNAmAge; b) blood age acceleration (AgeAcc) defined as the difference between DNAmAge and chronological age, but not TL, highly correlates with lung AgeAcc; c) blood AgeAcc significantly correlates with the main clinical features (CRP and FEV1) of COPD. 3) HEALTHY SUBJECTS AND PATIENTS EXPOSED TO REJUVENATING FACTORS - In healthy subjects but not in patients, DNAmAge is reduced after an intensive relaxing training. Differently, LTL is preserved in healthy subjects, while in patients it continues to decrease. However, the correlation between LTL and chronological age becomes positive after training in both groups. These findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. - Biological donors’ heart age is found to be younger than chronological age, suggesting that donors’ cardiac tissues are biologically younger than chronologically measured. Furthermore, biological donors’ left atrium age is 5 years younger than recipients’ left atrium age. This would indicate that patients who underwent heart transplantation have received a younger heart. Further results and comments are described in each work reported in the specific Chapters. Our results contribute to reinforce the concept that biological aging may be modulated by a multiplicity of factors (environmental, occupational, lifestyle) making people more susceptible to premature aging or inducing an accelerated aging or, interestingly, eliciting a rejuvenation effect. In the era of the silver tsunami, identifying gerontogenic and rejuvenating factors is of paramount importance to develop anti-aging strategies for extending the number of healthy years of life

Exploring mechanisms of biological aging in susceptible subjects

The aim of the PhD project is to explore molecular mechanisms that characterize the process of biological aging with the main focus on the two most prominent early hallmarks of biological aging such as telomere length (TL) and epigenetic age, also defined as DNA methylation age (DNAmAge), in order to answer the following main questions: 1) If environmental and occupational exposures accelerate the biological aging in healthy subjects and in subjects affected by age-relate disease. 2) If, on the other hand, correct lifestyle including an intensive meditation/relaxing training in healthy subjects and patients with cardiovascular diseases, and heart transplantation in patients suffering from end-stage heart failure, slow down biological aging. To this aims we analyzed biological aging indicators in easily available human tissue (blood leucocytes) and in target organ (i.e., heart of donors and recipients and lung from induced sputum of Chronic Obstructive Pulmonary Disease (COPD) patients). Study populations consist of: 1) HEALTHY SUBJECTS EXPOSED TO GERONTOGENIC ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES a) 71 night-shift workers and 84 day workers as control exposed to circadian rhythm disruption. b) 585 individuals from general population living in North-East Italy exposed to everyday exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution. c) A prospective cohort study of women and men aged 70 years and older from the area of Treviso, which is characterized by the highest longevity in Italy. TRELONG longitudinal study population comprises 576 subjects at baseline, 300 and 200 subjects at T1 and T2 respectively, exposed to lifestyle and occupational exposures. 2) SUBJECTS AFFECTED BY AGE-RELATE DISEASES a) Bladder cancer (BC), a chronic disease characterized by the interaction between environmental/occupational and genetic risk factors. Study population includes newly diagnosed, histologically confirmed BC patients, admitted to the Urology Departments of two large hospitals from 1997 to 2000. Controls are 94 non-neoplastic urological patients matched to cases by age, period and hospital of admission. b) Idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD) as the most common manifestations of aging-mediated diseases. Study population consists of n=101 IPF patients (ATS/ERS/JRS/ALAT guidelines) and n=18 moderate COPD patients (GOLD 2019) all enrolled at the ambulatory of Pneumology and Respiratory Physiopathology Wards – Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova. 3) HEALTHY SUBJECTS AND PATIENTS EXPOSED TO REJUVENATING FACTORS a) Patients after myocardial infarction (n=20) and healthy control individuals (n=10), age- and gender-matched, trained to meditation and relax for 60 days. b) 17 recipients receiving the heart from 17 donors in the period February 2018 - February 2019. The local Ethics Committee - University of Padova, approved the study protocols (3843/AO/16 and 3054/AO/14). Main finding stemming from our results revels that: 1) HEALTHY SUBJECTS EXPOSED TO GERONTOGENIC ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES - Night-shift work is associated with increased systemic inflammation as proved by higher C-reactive protein (CRP) levels among night shift workers. LTL is reduced by CRP, while is positively associated with long pentraxin 3 (PTX3) that, by orchestrating an efficient governance of inflammatory processes, may protect telomere from attrition. This would make nocturnal workers more susceptible to premature LTL shortening and aging. - Certain preventable everyday life exposures to PAHs diminish LTL and even LmtDNAcn, in particular in males, acting through anti-B[a]PDE–DNA adduct formation. Our findings show that indoor activities and diet represent the primary determinants of PAHs exposure in increasing anti-B[a]PDE–DNA adduct levels that in turn decrease in presence of detoxifying GSTM1. - In TRELONG population LTL significantly declines over the years, from baseline to follow up, also considering only n=161 subjects whit all measurements at three different time points. 2) SUBJECTS AFFECTED BY AGE-RELATE DISEASES - LTL attrition is a critical event in BC. In particular, BC risk is increased directly by LTL attrition that depends on some preventable everyday life exposures genetically modulated. Furthermore, indirect effects on BC risk are evidenced via LTL reduction through age and genetic polymorphisms involved in modulating response to environmental exposure. - IPF patients in follow up present an increase in LTL positively related to the duration of antifibrotic treatment, with both pirfenidone and nintedanib, and with a decrease in lung function decline. These results would suggest that telomere shortening in IPF patients treated with antifibrotic drugs may be reversed leading to an increase in LTL. - In COPD patients: a) lung, i.e., pulmonary cells obtained from induced sputum, is biologically older than blood, as determined by TL and DNAmAge; b) blood age acceleration (AgeAcc) defined as the difference between DNAmAge and chronological age, but not TL, highly correlates with lung AgeAcc; c) blood AgeAcc significantly correlates with the main clinical features (CRP and FEV1) of COPD. 3) HEALTHY SUBJECTS AND PATIENTS EXPOSED TO REJUVENATING FACTORS - In healthy subjects but not in patients, DNAmAge is reduced after an intensive relaxing training. Differently, LTL is preserved in healthy subjects, while in patients it continues to decrease. However, the correlation between LTL and chronological age becomes positive after training in both groups. These findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. - Biological donors’ heart age is found to be younger than chronological age, suggesting that donors’ cardiac tissues are biologically younger than chronologically measured. Furthermore, biological donors’ left atrium age is 5 years younger than recipients’ left atrium age. This would indicate that patients who underwent heart transplantation have received a younger heart. Further results and comments are described in each work reported in the specific Chapters. Our results contribute to reinforce the concept that biological aging may be modulated by a multiplicity of factors (environmental, occupational, lifestyle) making people more susceptible to premature aging or inducing an accelerated aging or, interestingly, eliciting a rejuvenation effect. In the era of the silver tsunami, identifying gerontogenic and rejuvenating factors is of paramount importance to develop anti-aging strategies for extending the number of healthy years of life

The effect of low birth weight as an intrauterine exposure on the early onset of sarcopenia through possible molecular pathways

Abstract 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