Search Results (130)

DNA methylation clocks provide a tractable molecular readout for testing whether nutritional and natural-product interventions can modify biological aging. Natural-product-derived antioxidants are biologically plausible candidates because they influence redox signaling, inflammation, mitochondrial function, microbial metabolism and epigenetic regulation, yet their effects on DNA methylation-based aging remain difficult to interpret. Here, we systematically synthesize human intervention studies evaluating antioxidant-rich dietary patterns, botanical and food-derived extracts, marine omega-3 fatty acids, multi-component nutraceuticals and related lifestyle-based interventions with DNA methylation-clock outcomes. The available evidence does not support a uniform epigenetic anti-aging effect. Instead, methylation-age responses were clock-specific, exposure-dependent and often most apparent in metabolically or biologically responsive subgroups. Longer randomized or trial-embedded studies provided the most credible signals, whereas small uncontrolled studies mainly generated hypotheses. Future trials should move beyond claims of epigenetic age reversal and test whether objectively verified natural-product-derived antioxidant exposures produce reproducible, mechanistically linked, and clinically meaningful changes in aging biology. Full article

Aptamer-based multiplexed proteomic platforms, especially the SOMAmer-based SomaScan assay, are widely used for large-scale discovery of circulating biomarkers relevant to human aging. This review summarizes 42 original research articles published from 2020 through 2026 in which aptamers or aptamer-derived biosensors were used to characterize aging-related biomarkers in human samples or clinically relevant human-disease contexts. The eligible literature falls into several thematic areas: whole-plasma and organ-specific proteomic aging clocks; inflammaging and senescence-associated secretory phenotype (SASP) markers; cardiovascular, metabolic, renal, hepatic, musculoskeletal and neurodegenerative biomarker panels; and aptasensor platforms for detection of individual analytes. Only a small number of studies have compared aptamer- and antibody-based platforms in the same specimens; we tabulate these and show that median between-platform agreement is low to moderate, which constrains the pooling of findings across technologies. We also make explicit an interpretive point that is usually left implicit: because proteomic clocks are trained against chronological age, their correlation with chronological age measures fit to the training target rather than biological validity, and the informative quantity is the residual age gap. In the reviewed literature, SomaScan-based studies are concentrated in cardiovascular, neurodegenerative, frailty, and proteomic aging-clock research, whereas de novo SELEX campaigns targeting aging-specific epitopes and longitudinal human validation of wearable aptasensors were not identified. The main barriers to translation are cross-platform discordance, limited replication across ancestries, under-reported pre-analytical variability, cost, and the research-use-only status of most assays. Full article

Background: Precision nutrition and nutrigenomics have emerged as promising strategies to personalize dietary interventions according to individual genetic, metabolic, and molecular characteristics. However, the potential of nutrigenomic-guided nutraceutical interventions to modulate biological aging pathways remains poorly characterized. Objective: This study aimed to map and synthesize the available evidence from human studies evaluating personalized nutraceutical interventions based on nutrigenomic approaches and their effects on biomarkers associated with biological aging. Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched for studies published between 2021 and 2026. Eligible studies included adults aged ≥18 years receiving personalized nutraceutical interventions informed by genetic, genomic, metabolomic, or other molecular data. Outcomes included biomarkers of cellular aging, inflammation, oxidative stress, immunometabolism, and related pathways. Results: Twenty-one studies were included. Interventions involved omega-3 fatty acids, polyphenols, Nigella sativa, vitamin D, methyl-donor micronutrients, fermented papaya preparation, and other nutraceutical preparations and functional food-based interventions. Four major themes emerged: multi-omic stratification approaches, biological aging biomarkers, redox-inflammatory modulation, and applications in metabolic disorders. Most studies demonstrated favorable effects on intermediate molecular biomarkers, including inflammatory cytokines, oxidative stress markers, lipid metabolism, endothelial function, and DNA methylation signatures. However, evidence directly demonstrating slowing of biological aging through validated biomarkers such as epigenetic clocks or telomere dynamics remains limited. Conclusions: Personalized nutraceutical interventions exhibit biological plausibility for modulating pathways associated with healthy aging. Nevertheless, robust longitudinal studies incorporating validated biomarkers of biological aging and clinically meaningful outcomes are needed before their widespread implementation in precision medicine. Full article

Background: DNA methylation is a key epigenetic mechanism whose dynamics are closely linked to ageing. Modern epigenetic clocks predict biological age based on the average methylation level. The concept of “epigenetic rejuvenation” posits that at early stages of development, the biological age of the embryo may decrease, reaching a minimum (“ground zero”) at the gastrulation stage. However, standard averaging methods may not account for important rearrangements in the internal structure of methylation. Objective: To apply the apparatus of information theory and topological data science to the analysis of scNMT-seq data and to test whether DNA methylation entropy decreases from stage E4.5 to E6.5, which would correspond to an approach towards the biological zero state. Methods: Publicly available scNMT-seq data (GSE121690) were analyzed. Five entropy measures were calculated for each cell (Shannon, Renyi, Tsallis, LZ-complexity, local gradient entropy (entropy of variations in the smoothed histogram of the methylation distribution), and persistent entropy (PE)—a topological complexity measure). For the five-dimensional entropy feature space, a Rips complex was constructed, and persistence diagrams H_0 and H_1 were computed. Results: All five entropy measures decreased significantly, with LZ complexity showing the largest relative reduction (−28.4%) and the strongest independent signal (partial r = −0.181). Among all the complexity measures studied, LZ complexity exhibited the largest relative reduction, underscoring its heightened sensitivity to the progressive ordering of the epigenetic landscape. Notably, the ternary encoding of LZ complexity showed strong correlation with Shannon entropy (r = 0.71), indicating that algorithmic complexity, when accounting for partial methylation states, aligns closely with statistical entropy while retaining sensitivity to spatial order. The consistency of results across binary and ternary encodings confirms the robustness of LZ complexity as a structural biomarker. Persistent entropy confirmed the general dynamics (decrease from 15.91 to 14.89, p = 0.01). Topological analysis of the multidimensional space revealed a qualitative reorganization: at stage E6.5, stable cyclic structures (H₁) emerge, while at E4.5 the space is dominated by a single large-scale cycle. Null model validation confirmed that the observed H₁-cycles are genuine topological features rather than random fluctuations. Comprehensive topological characterization showed that normalized persistent entropy increases from 0.846 to 0.882 (p < 0.001), while maximum persistence decreases from 0.446 to 0.218 (p < 0.001), reflecting a transition from a homogeneous state to structured diversification—multiple, evenly distributed cycles corresponding to distinct cell lineages. Consistent with this, regional disorder (RE/RD) at the single-cell level decreases from E4.5 to E6.5 (RE: −25.5%, RD: −27.4%, p < 10⁻¹³), while global entropy also decreases, together painting a picture of epigenetic rejuvenation as ordered consolidation at the whole-genome scale. An SVM model trained on 15 entropy and structural features achieved stage classification with an accuracy of 93.4% and AUC of 0.981, confirming the diagnostic potential of the approach. Conclusions: The decrease in DNA methylation entropy from E4.5 to E6.5 corresponds to an approach to “ground zero”—the point of minimum biological age in embryogenesis—and supports the hypothesis of a link between decreasing entropy and epigenetic rejuvenation. The addition of topological analysis reveals the hidden organization of epigenetic diversity, showing that ordering does not lead to homogenization but is accompanied by the formation of distinguishable cell lineages. Full article

Metabolomic aging clocks—quantitative models that estimate biological age based on small-molecule profiles in biological fluids—have become dynamic tools for assessing individual aging trajectories and predicting the risk of age-related diseases. Although NMR-based approaches have been previously reviewed, the analytical landscape of mass spectrometry (MS)-based metabolomic clocks has not been systematically assessed. This review examines the key components of the MS-based analytical workflow underlying the development of metabolomic aging clocks, including biological matrix selection, chromatographic separation strategies, MS instrumentation, data preprocessing, metabolite annotation, and machine learning-based modeling approaches. Twelve published studies on MS-based metabolomic clocks were identified and systematically compared. These clocks provide predictions of chronological age with mean absolute errors of 3.5–10 years and demonstrate robust associations between metabolomic age acceleration and cardiometabolic risk, frailty, and mortality. Recurrent age-related metabolite classes include tryptophan–kynurenine pathway metabolites, acylcarnitines, sphingolipids, modified nucleosides, and tricarboxylic acid (TCA) cycle intermediates. Currently, liquid chromatography with electrospray ionization (LC-ESI) coupled to high-resolution QTOF or Orbitrap instruments dominates current workflows, with elastic net regression being the most commonly applied modeling strategy. Significant heterogeneity in analytical conditions, incomplete methodological descriptions, and limited cross-study validation remain key obstacles to clinical application. Standardization of pre-analytical protocols, the use of certified reference materials, and harmonized validation frameworks are identified as critical priorities for advancing mass spectrometry-based metabolomic clocks toward clinical translation. Full article

Background: Visceral obesity is increasingly recognised not as a simple excess of adipose tissue, but as a systemic pathological condition characterised by profound metabolic, endocrine, and immune dysregulation. Visceral adipose tissue (VAT) operates as an autonomous neuro-immune-endocrine organ whose dysfunctional expansion drives insulin resistance, atherogenesis, and accelerated cellular ageing through mechanisms converging on chronic low-grade sterile inflammation, referred to as inflammaging. Objectives: This narrative review integrates evidence across four domains: (1) the multi-system clinical complications of visceral obesity and the methodological controversies surrounding its measurement; (2) the cellular heterogeneity, immunometabolic reprogramming, and molecular mechanisms through which excess VAT accelerates biological ageing, with a focus on genomic instability, mitochondrial dysfunction, the NAD⁺/sirtuin regulatory axis, cellular senescence, and inter-organ communication; (3) the role of bioelectrical impedance analysis (BIA)—particularly phase angle—as a non-invasive functional biomarker of biological age and longevity, positioned critically against alternative assessment methods; and (4) current knowledge gaps and priorities for future research. Methods: A narrative review of PubMed/MEDLINE, Google Scholar, and the Cochrane Library was conducted using MeSH terms and free-text keywords including visceral obesity, bioelectrical impedance analysis, phase angle, sarcopenia, inflammaging, mitochondrial dysfunction, cellular senescence, epigenetic clocks, NAD⁺, sirtuin, and longevity, supplemented by citation-tracking of retrieved reviews. English-language articles published up to April 2025 were considered, prioritising systematic reviews, meta-analyses, and prospective cohort studies; formal risk-of-bias tools and quantitative synthesis were not applied, consistent with a narrative review design. Results and Discussion: BIA-derived phase angle constitutes a macroscopic electrobiological correlate of inflammaging: low phase angle values in visceral obese subjects overlap with those of frail elderly individuals, reflecting impaired membrane integrity, loss of active cell mass, and altered ICW/ECW balance. However, this evidence base remains largely cross-sectional and correlative; the directionality and population-specific calibration of BIA-derived indices constitute the principal unresolved methodological questions. Integration with epigenetic clocks, circulating NAD⁺ levels, and gut microbiome indices offers a framework for dynamic biological age assessment, though prospective interventional validation is still lacking. Sarcopenic obesity, evaluated through EWGSOP2 combined with BIA-derived skeletal muscle mass index and handgrip dynamometry, represents a critical comorbidity demanding integrated therapeutic targeting. Conclusions: BIA provides a quantitative, accessible correlate for translating cellular metabolic health into clinically actionable parameters, complementary to rather than a replacement for anthropometric and imaging-based methods. Optimising phase angle and reducing VAT through anti-inflammatory nutrition, exercise, and nutraceutical strategies targeting the NAD⁺/sirtuin and mTOR/AMPK axes constitutes a measurable objective for the promotion of healthy longevity, contingent on the longitudinal, mechanistic studies identified as priorities in this review. Full article

Residential greenness has been consistently associated with multiple health benefits; however, the underlying molecular mechanisms remain insufficiently understood. DNA methylation-based epigenetic clocks have emerged as robust biomarkers of biological aging and provide a valuable framework for investigating environmental influences on aging processes. This systematic review synthesizes current human evidence linking greenspace exposure to epigenetic age acceleration and DNA methylation changes. Following PRISMA 2020 guidelines, we searched Scopus and Web of Science databases (inception to May 2026). Studies were eligible if they assessed quantitative indicators of greenspace exposure and DNA methylation-based aging biomarkers in human populations. Out of 97 identified records, 14 studies met the inclusion criteria. Higher levels of greenspace exposure were consistently associated with a deceleration of GrimAge acceleration, with effect sizes ranging from 1.0 to 1.6 years per interquartile range increase in greenness. At the molecular level, greenspace-associated differentially methylated regions (DMRs) were consistently enriched in genes involved in neurodevelopment (HTR2A, BDNF, SLC6A3, SDK1), immune regulation (HLA-DRB5, IL6), stress response (NR3C1), and extracellular matrix remodeling (ADAMTS2). Overall, greenspace exposure is associated with slower epigenetic aging and differential DNA methylation across key biological pathways. These findings support the concept of greenspace as an epigenomic resilience factor and highlight its potential role in modulating molecular mechanisms of aging. Full article

Age-related changes in neurotransmitter systems contribute to declines in cognitive, emotional, and motor function, yet the biological mechanisms linking these changes to aging are not completely understood. Epigenetic regulation offers a promising framework to bridge this gap. DNA methylation-based biomarkers of biological aging (i.e., epigenetic clocks) capture cumulative and dynamic aspects of biological aging that may reflect vulnerability in neural systems beyond chronological age. However, whether these indices track with the integrity of neurotransmitter systems has not been systematically examined. This scoping review synthesizes evidence across human studies to evaluate how epigenetic aging processes influence neurotransmitter gene regulation and system function across the lifespan. We included 109 studies spanning 2005–2026. GABAergic genes (GAD1, GABRA2) showed the most consistent and reproducible age-related promoter hypermethylation across the cortex, inversely correlated with mRNA expression and corroborated by MRS evidence of cortical GABA decline. Dopaminergic and serotonergic evidence during normative aging was sparse; most epigenetic data in these systems came from disease cohorts. Histone modifications converged on neurotransmission and synaptic-plasticity loci, predominantly in Alzheimer’s disease tissue. Subcortical and brainstem nuclei central to monoaminergic and cholinergic systems remain under-investigated for normative aging epigenetic processes. Environmental and social determinants, socioeconomic status, childhood adversity, and chronic stress, were consistently associated with accelerated peripheral epigenetic aging, but brain-specific data are scarce. Full article

Aging is a major risk factor for numerous chronic diseases and a leading contributor to global mortality. Slowing the rate of aging would have revolutionary implications for health and longevity. A fundamental barrier to achieving this goal, however, is the difficulty of accurately measuring the effects of rejuvenating interventions. The development of precise gerontometric methods, therefore, is a priority for both science and preventive medicine. In this opinion article, the authors suggest the principles and discuss the implementation of precision gerontometry using recent advances in metabolomics. Although metabolomic approaches have limited accuracy in determining biological age, the described approach, which averages multiple metabolites from a large metabolomic signature of aging, circumvents this limitation. It allows for measurement of biological age change with an accuracy of approximately one month. Such precision gerontometry enables accelerated testing of candidate anti-aging interventions, helping to eliminate ineffective ones, speed the development of effective ones, and ultimately extend the duration of healthy human life, with profound social and humanitarian benefits. Full article

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article

Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability. Full article

Chronological age is a poor indicator of interindividual differences in biological aging. DNA methylation-based epigenetic clocks provide a reliable measure of biological age and epigenetic age acceleration (EAA). Although modifiable behavioral, environmental, and social factors appear to influence EAA, the magnitude, consistency, and potential preventability of these associations have never been systematically quantified. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed/MEDLINE and Scopus were searched from inception to 7 April 2026 for English-language observational and interventional studies reporting quantitative associations between modifiable determinants and EAA measured using validated clocks (Horvath, PhenoAge, GrimAge, DunedinPACE). Effect sizes were harmonized into four analytical pools. Random-effects meta-analyses were performed using the DerSimonian–Laird estimator, with pre-specified subgroup analyses by exposure category. Heterogeneity, publication bias, and robustness were thoroughly assessed. A novel Modifiable Epigenetic Aging Burden Index (MEAB-Index) was developed to quantify the cumulative preventable burden. Only studies conducted in adult populations (≥18 years) were eligible. Eighty-three studies providing 118 distinct exposure–clock associations were included. In the primary analysis (Pool A, n = 60), adverse modifiable exposures were associated with accelerated EAA (pooled β = +0.310 years per unit exposure, 95% CI 0.255–0.366). The strongest associations were observed for metabolic and inflammatory markers (β = +0.913) and environmental exposures (β = +0.466). The MEAB-Index yielded a Cumulative Preventable Burden of +1.566 years (bootstrap 95% CI 1.011–2.123). Findings were robust across sensitivity analyses and remained directionally consistent in secondary pools (B–D). This study provides the most comprehensive quantitative synthesis to date on the modifiability of epigenetic aging. Our findings demonstrate that EAA is meaningfully shaped by behavioral, environmental, and social determinants. The MEAB-Index introduces a novel framework for estimating the preventable burden of biological aging and for prioritizing interventions. Reducing key modifiable risk factors, particularly metabolic/inflammatory and environmental exposures, could substantially slow biological aging at the population level and support the transition toward ageing-centered preventive strategies. Full article

Background/Objectives: Spaceflight presents a combination of physical and psychosocial stressors that may impact biological aging and health. Understanding how spaceflight influences molecular aging processes is essential as commercial and professional space travel continue to expand. Methods: We analyzed publicly available DNA methylation data to evaluate longitudinal changes in 10 epigenetic aging biomarkers, 6 leukocyte proportion estimates, and 109 DNA methylation-derived protein scores in two astronauts participating in Axiom Space’s AX1 17-day low Earth orbit mission. We calculated mean values for all biomarkers across three timepoints: two weeks before spaceflight (T0), 24 h after spaceflight (T1), and three months after spaceflight (T2). Using the mean values, we next calculated the fold change from baseline for all biomarkers. Because the sample size precluded statistical testing, we identified the top 5% of absolute fold changes to highlight the largest shifts across candidate biomarkers. Results: Across epigenetic clocks, MiAge showed the greatest T0–T1 decrease (−4.26-fold), and DNAmFitAge showed the greatest T0–T2 increase (2.47-fold). NK cells exhibited the largest T0–T1 change, decreasing by 49% (−0.49-fold). B cells exhibited the largest T0–T2 change, decreasing by 11% (−0.11-fold). Proteins meeting a predefined top 5% fold change from baseline criterion at both T1 and T2, included BMP1, CLEC11A, CXCL11, FAP, and LTF. Enrichment analysis indicated involvement of serine-type endopeptidase activity, molecular function activator activity, and cell aggregation pathways. Conclusions: These findings suggest that spaceflight influences methylation-derived biomarkers of aging and immunity even in short-duration missions. These results, though exploratory, contribute to emerging efforts to characterize molecular resilience and vulnerability in human spaceflight. Full article

Environmental contaminants such as per- and polyfluoroalkyl substances (PFAS) and toxic metals have been implicated in biological aging, yet their combined effects remain poorly understood. This study evaluated the associations of PFAS, lead, and cadmium mixtures with multiple DNA methylation-based measures of epigenetic aging in a nationally representative sample of U.S. adults aged ≥ 50 years. Data were obtained from the 1999–2000 and 2001–2002 National Health and Nutrition Examination Survey (NHANES). The analytic sample included 1119 participants with available data on seven PFAS, blood lead, cadmium, and DNA methylation measures. Epigenetic aging outcomes included HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge, and DunedinPoAm. Multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) were used to assess individual and joint exposure–response relationships. Cadmium showed the most consistent positive associations with epigenetic aging measures, particularly for the second-generation clocks PhenoAge and GrimAge. Lead was positively associated with GrimAge, while PFAS showed more variable and generally weaker associations, with PFNA demonstrating the most consistent signal. Mixture analyses indicated that higher combined exposure levels were associated with higher DNA methylation age estimates, with stronger patterns observed for second-generation clocks. These findings suggest that combined exposure to PFAS, lead, and cadmium is associated with higher epigenetic aging in older U.S. adults, with cadmium emerging as a key contributor to the observed mixture effects. Evaluating environmental exposures as mixtures may provide important insight into how co-occurring contaminants jointly influence biological aging. Full article

Skin aging is a complex, multifactorial process driven by intrinsic biological mechanisms and environmental exposures, resulting in progressive functional and structural decline. Chronological age does not adequately capture this variability, highlighting the need for molecular biomarkers that reflect biological aging. In this context, transcriptomic aging clocks have emerged as a promising approach, as gene-expression profiles provide a dynamic representation of cellular and tissue states. This narrative review is based on a targeted literature search in PubMed and IEEE Xplore and focuses on transcriptomic aging clocks in human skin, with emphasis on gene-expression signatures, key biological pathways, and computational modeling strategies. These models consistently capture coordinated alterations in processes such as cellular senescence, DNA damage response, inflammation, and extracellular matrix remodeling. Representative transcriptomic frameworks, including models such as SkinAGE, illustrate the ability of gene-expression-based approaches to quantify biologically meaningful and dynamic aging states in the skin. Advances in machine-learning approaches, including deep learning and pathway-guided models, are critically evaluated, alongside the role of explainable artificial intelligence in enhancing model transparency and biological interpretability. Future developments are expected to integrate multi-omics data and digital twin frameworks, enabling the transition from static biomarkers toward dynamic, predictive, and personalized models of skin aging. Full article