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        <title>Frontiers in Aging | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/aging</link>
        <description>RSS Feed for Frontiers in Aging | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-06-24T19:24:04.908+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1763012</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1763012</link>
        <title><![CDATA[Development of the social frailty scale for older adults under pandemic-related social restrictions]]></title>
        <pubdate>2026-06-24T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Pei-Hsin Fang</author><author>Ray-E. Chang</author><author>Robert C. Myrtle</author><author>Ying-Hui Hou</author><author>Ya-Mei Chen</author>
        <description><![CDATA[IntroductionSocial frailty, a key dimension of the multidimensional assessment of frailty, has been linked to poor health outcomes and poorer quality of life in older adults. However, definitions and measurements of social frailty vary and most do not provide assessments of reliability or validity. This study sought to identify the core components associated with social frailty and to create a reliable, valid social frailty scale.MethodsThis study adopts a psychometric approach to develop a social frailty scale for use in a community context under pandemic-related social restrictions. Systematic searching, content analysis, and a modified Delphi method were applied to develop a draft of a social frailty scale. Item-analysis, explorative factor analysis, confirmatory factor analysis, and reliability analysis were used to test scale properties. The subjects were older adults above 65 years old who live in Taiwan, and 446 people in total were interviewed to collect data.ResultsThe results indicated that five factors (two types of social support, social participation, social networks, and loneliness) and 16 items formed a social frailty scale with appropriate reliability and validity. This study advances our understanding of core components of social frailty.DiscussionThe social frailty scale integrates several social frailty instruments to detect social frailty in community context.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1813553</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1813553</link>
        <title><![CDATA[Extracellular vesicles as minimally invasive biomarkers and therapeutic platforms in rare neurological diseases]]></title>
        <pubdate>2026-06-24T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Nathan D. Phan</author><author>Raghu Rai Sharma</author><author>Subbaya Subramanian</author><author>Reena V. Kartha</author>
        <description><![CDATA[Rare neurological diseases (RND) represent a growing but underrecognized global health burden, particularly in aging populations in whom clinical manifestations appear later in life, resulting in substantial morbidity, reduced quality of life, and increased mortality. Advances in understanding and treating these diseases have been hindered by low prevalence, phenotypic heterogeneity, and complex molecular mechanisms. Importantly, shared genetic and mechanistic links between rare and common neurodegenerative disorders, such as GBA1 (Glucosylceramidase Beta 1) gene variant-associated Gaucher disease (GD) and Parkinson’s disease (PD), highlight convergent biological pathways that may be leveraged for biomarker discovery and therapeutic innovation. Notably, individuals heterozygous for pathogenic GBA1 variants, historically considered asymptomatic carriers, are now recognized to have an increased lifetime risk of developing PD and related synucleinopathies. This emerging evidence indicates that even single-allele variants can confer long-term neurological risk, reinforcing the continuum between rare monogenic disorders and more common neurodegenerative diseases. Extracellular Vesicles (EVs) have emerged as a promising, minimally invasive platform for advancing RND research, although translation remains limited by source specificity, vesicle heterogeneity, and incomplete clinical validation. By encapsulating proteins, lipids, and nucleic acids that reflect their cellular origin and disease state, EVs offer unique opportunities for early diagnosis, disease stratification, longitudinal monitoring, and assessment of treatment responses. In this review, we summarize fundamental aspects of EV biology and critically evaluate recent advances in EV-based biomarker discovery for RND, informed by translational insights from more prevalent neurodegenerative conditions. We further discuss the therapeutic potential of EVs, emphasizing their intrinsic biocompatibility, their reported capacity in selected preclinical settings to traverse biological barriers, including the blood-brain barrier, and their versatility as carriers for neuroprotective and gene-modifying cargo. Finally, we address key technical and translational challenges, including isolation, characterization, scalability, and regulatory considerations that currently limit clinical adoption. Collectively, this review highlights emerging opportunities and outlines an integrative translational perspective for EV-based diagnostic and therapeutic strategies into research and clinical paradigms for aging individuals affected by RND.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1830839</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1830839</link>
        <title><![CDATA[Mitochondrial transcription factor A: linking mtDNA maintenance, mitochondrial stress responses, and inflammaging]]></title>
        <pubdate>2026-06-24T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Nengneng Shi</author><author>Xiaojing Li</author>
        <description><![CDATA[Mitochondrial transcription factor A (TFAM) is a nuclear-encoded mitochondrial protein that directly binds mitochondrial DNA (mtDNA) and contributes to mitochondrial genome maintenance. Beyond its established roles in mitochondrial transcription, mtDNA packaging, nucleoid organization, replication support, and copy number control, TFAM is increasingly recognized as a potential regulator of aging-related mitochondrial stress responses. Because mtDNA instability, respiratory dysfunction, reactive oxygen species imbalance, impaired autophagy, cellular senescence, and chronic inflammation are closely interconnected during aging, TFAM may occupy a proximal position linking mitochondrial genome homeostasis to broader aging biology. However, TFAM should not be viewed as a uniformly protective factor. Its effects appear to depend on TFAM abundance, TFAM-to-mtDNA stoichiometry, tissue type, metabolic state, mitochondrial import, LONP1-mediated turnover, and mitochondrial quality-control capacity. TFAM deficiency may compromise mtDNA maintenance, impair oxidative phosphorylation, increase mitochondrial ROS production, and promote mtDNA-driven innate immune activation. Conversely, excessive or dysregulated TFAM accumulation may lead to mtDNA hypercompaction, reduce mtDNA accessibility, and potentially produce maladaptive effects in specific disease contexts. In this review, we discuss the structural basis of TFAM–mtDNA interaction, the role of TFAM in mtDNA transcription, copy number control, genome protection, damage handling, inflammatory signaling, cellular senescence, systemic aging, and age-related diseases. We also highlight therapeutic opportunities, limitations, and unresolved questions, emphasizing that future strategies should aim to restore TFAM homeostasis rather than simply increase TFAM expression.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1842955</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1842955</link>
        <title><![CDATA[Resetting the epigenetic clock: cellular senescence and regenerative strategies in intervertebral disc degeneration]]></title>
        <pubdate>2026-06-17T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Minfan Li</author><author>Haitao Deng</author><author>Hongda Xu</author><author>Qingzhong Zhou</author><author>Shengxin Zhao</author>
        <description><![CDATA[Intervertebral disc degeneration (IDD) is the leading pathological cause of low back pain, while current clinical treatments are only palliative and cannot reverse the programmed cellular senescence driven by epigenetic dysregulation. This process is characterized by progressive loss of nucleus pulposus (NP) cell identity and establishment of a self-amplifying senescence-associated microenvironment. In this review, we synthesize recent advances elucidating how heterogeneous senescent cell populations and their secretory phenotype (SASP) orchestrate a destructive vicious cycle in IDD. We further dissect the synergistic interplay among DNA methylation, histone modifications, and non-coding RNAs that constitutes the “epigenetic aging clock” and drives premature cellular aging within the disc. Notably, we evaluate emerging therapeutic strategies aimed at clock reversal, including senolytic clearance of senescent cells, epigenetic remodeling using small-molecule inhibitors or CRISPR-dCas9 editing, and cellular reprogramming approaches ranging from iPSC differentiation to direct lineage conversion. We propose a synergistic “clear, prime, then seed” roadmap that sequentially combines these interventions for optimal regeneration. This work provides a systematic theoretical framework for the clinical translation of epigenetic-targeted therapy for IDD, and breaks through the cognitive limitation of traditional mechanical wear theory.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1890954</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1890954</link>
        <title><![CDATA[Editorial: Microbial influences on aging: insights from the gut microbiome]]></title>
        <pubdate>2026-06-17T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Christina Tsigalou</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1822471</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1822471</link>
        <title><![CDATA[The impact of the six pillars of lifestyle medicine on the biology of skin aging]]></title>
        <pubdate>2026-06-17T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Jaime Piquero-Casals</author><author>Adriana R. Cruz</author><author>Lucas Ponti-Concetti</author><author>Ludmila Prudkin</author><author>Anthony Brown</author><author>Mónica Foyaca</author><author>Eduardo Rozas-Muñoz</author><author>Juan Francisco Mir-Bonafé</author><author>Daniel Morgado-Carrasco</author><author>Thierry Passeron</author>
        <description><![CDATA[Skin aging arises from the interaction between intrinsic genetic programs and cumulative environmental and behavioral exposures collectively defined as the exposome. Increasing evidence indicates that core molecular pathways driving skin aging, including mitochondrial dysfunction, oxidative stress, chronic inflammation, cellular senescence, and extracellular matrix remodeling are responsive to modifiable lifestyle factors. This narrative review examines the mechanistic and translational evidence linking the six pillars of Lifestyle Medicine; nutrition, physical activity, stress regulation, sleep, avoidance of toxic exposures, and social connection, to fundamental biological processes involved in skin aging. Across experimental models and human studies, these lifestyle domains converge on established hallmarks of aging, modulating redox balance, inflammatory signaling, mitochondrial biogenesis, epigenetic regulation, DNA repair, and dermal matrix integrity. Nutritional patterns influence glycation and oxidative stress; physical activity enhances mitochondrial and vascular function; chronic stress and sleep disruption amplify neuroendocrine and inflammatory pathways; toxic exposures activate matrix-degrading and senescence-associated cascades; and social isolation is associated with heightened systemic inflammatory tone. Collectively, these findings support the concept that skin aging represents a biologically plastic process shaped in part by lifestyle-dependent modulation of conserved aging mechanisms. Integrating lifestyle-responsive pathways into skin aging research may enable more targeted, preventive, and mechanism-based strategies in dermatological practice.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1825900</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1825900</link>
        <title><![CDATA[Cardiovascular health assessed by life’s essential 8 in Israeli adults aged ≥65 years and its association with long-term cancer incidence]]></title>
        <pubdate>2026-06-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ahmad Marzooq</author><author>Samah Hayek</author><author>Yariv Gerber</author>
        <description><![CDATA[BackgroundCardiovascular disease (CVD) and cancer, leading causes of morbidity and mortality in an aging global population, share risk factors and frequently coexist. Their relationship remains incompletely understood, particularly regarding the link between cardiovascular health (CVH) and cancer incidence among older adults.ObjectiveTo examine the association between CVH, assessed using Life’s Essential 8 (LE8), a composite measure of health behaviors and cardiometabolic factors, and cancer incidence in a nationwide sample of older adults.MethodsA cohort of Israeli adults aged ≥65 from the 2005–2006 National Health and Nutrition Survey. Baseline health behaviors and CVD risk factors were used to categorize participants according to LE8. Cancer data were obtained from the National Cancer Registry through December 2019. Cause-specific Cox proportional hazards models estimated hazard ratios (HRs) for incident cancer, adjusting for sociodemographic variables.ResultsAmong cancer-free participants at baseline [n = 1543; mean age (SD), 75 (6) years; 53% women; 39% with pre-existing CVD], LE8 scores ranged from 7–97 [mean (SD), 56 (14)]. LE8 scores were positively associated with education and residential socioeconomic status and were lower among men and Arab participants. Over a median follow-up of 11.7 years, 345 participants (22%) were diagnosed with all-site cancer. LE8 was inversely associated with cancer incidence (adjusted HR = 0.88, 95% CI: 0.79–0.98 per 1 SD increase). The association was evident primarily among CVD-free participants (HR = 0.84, 95% CI: 0.74–0.97).ConclusionHigher LE8 scores were associated with lower long-term cancer incidence in older adults. These findings extend the relevance of LE8 beyond CVD prevention and suggest that maintaining favorable CVH in later life may be associated with a lower risk of cancer.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1736105</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1736105</link>
        <title><![CDATA[The effect of metformin treatment during primary influenza infection on heterologous challenge in young and aged mice]]></title>
        <pubdate>2026-06-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Dominique E. Teskey</author><author>Andreia N. Cadar</author><author>Nagaraju Marka</author><author>Zena L. Haddad</author><author>Darlene A. Djaba</author><author>Blake L. Torrance</author><author>Ferris El-Tayyeb</author><author>Bishajit Sarkar</author><author>Aadrita Hazra</author><author>Jenna M. Bartley</author>
        <description><![CDATA[IntroductionRespiratory illnesses like influenza and SARS-CoV-2 disproportionately affect older adults, leading to severe complications and high mortality rates. Age-related immune dysregulation impairs infection responses and hinders recovery. The geroscience hypothesis suggests that targeting biological aging can enhance overall healthspan. Mitochondrial dysfunction and dysregulated nutrient sensing, hallmarks of aging, profoundly affect metabolism and cellular function. Metformin, an FDA-approved diabetes drug, is a candidate anti-aging drug and has been shown to positively impact immune cell function in many contexts. However, the totality of these effects on immune cells remains under investigation. Here, we aim to determine if metformin treatment could improve immune memory responses by utilizing a heterologous flu challenge model.Methods Young and aged mice were given control or metformin treated chow for 6 weeks prior to being infected with a sublethal dose of H3N2 influenza virus A/HKx31 (X31). Control and treated chow continued until 10 days post infection to examine the effects of metformin on immune memory formation. Mice were then allowed to recover and at 30 days post initial infection and were challenged with a heterologous H1N1 influenza virus A/Puerto Rico/8/34 (PR8). Mice were sacrificed on day 0 (prior to secondary flu challenge), and at 5, 7, 10, and 14 days post-secondary infection to unveil changes in the kinetics of immune responses.ResultsMetformin altered only some aspects of immune responses during secondary flu challenge, and more so in young mice compared to aged mice. More specifically, we did not observe improved T cell memory populations in the lungs following primary flu infection in aged metformin treated mice compared to aged control treated mice. Moreover, while aged metformin treated mice had modestly improved weight loss during heterologous challenge, they had transiently increased lung viral load compared to aged control treated mice.Discussion This suggests that metformin could not overcome the totality of aging to improve T cell memory responses. Thus, while metformin has been shown to have many benefits in a variety of aging conditions, its specific utility in improving age-related declines in immune memory formation during infection is unclear in our studies. More research is necessary to determine how metformin can target aging physiology and T cell function to enhance immune responses, and importantly, understand the limitations of its utility in aging populations.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1843098</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1843098</link>
        <title><![CDATA[Effects of Kiperin Elixea, a multicomponent antioxidant supplement, on redox homeostasis and longevity-associated gene expression in human epithelial cell models]]></title>
        <pubdate>2026-06-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Lutfiye Karcıoğlu Batur</author><author>Ahsen Pektas</author><author>Buse Aslan</author><author>Nermin Akcali</author>
        <description><![CDATA[IntroductionAging is characterized by declining NAD+ levels, mitochondrial dysfunction and disruption of redox homeostasis. Multi-component formulations targeting interconnected hallmarks of aging have emerged as potential geroprotective strategies.MethodsWe evaluated the molecular and functional effects of Elixea, an NMN (nicotinamide mononucleotide)-based formulation containing NAD+ precursors (NMN, NADH), mitochondrial cofactors (CoQ10, PQQ), and antioxidants (resveratrol, glutathione), in human epithelial cell models. hTERT-HME1 and HaCaT cells were treated with 0.1 μg/mL Elixea for 24 h. Cellular viability, regenerative kinetics, total antioxidant status (TAS), total oxidant status (TOS), and expression of longevity-associated genes were assessed.ResultsElixea maintained normal cell viability and migration dynamics, supporting the preservation of basal epithelial function. In hTERT-HME1 cells, treatment significantly improved redox homeostasis, as evidenced by increased TAS and reduced TOS levels. Gene expression analysis revealed significant upregulation of IL10, FOXO3A, APOE, GPX1, and FOXO1A, indicating activation of pathways associated with antioxidant defense, anti-inflammatory signaling, and metabolic regulation. In HaCaT cells, responses were more selective, including upregulation of APOE, FOXO3A, and RUVBL1.DiscussionCollectively, these findings suggest that Elixea modulates conserved longevity-associated pathways in a cell type-dependent manner, promoting cellular resilience without evidence of cytotoxicity or overt stress-associated responses. This study provides mechanistic evidence supporting the geroprotective potential of multi-component interventions targeting redox and metabolic networks in epithelial systems.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1800288</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1800288</link>
        <title><![CDATA[Integrating evolutionary theory into a framework for the mechanistic evaluation of candidate anti-aging interventions]]></title>
        <pubdate>2026-06-15T00:00:00Z</pubdate>
        <category>Hypothesis and Theory</category>
        <author>Yusuf Aggour</author><author>Roberto Salguero-Gómez</author>
        <description><![CDATA[Despite decades of research into the molecular hallmarks of aging, geroscience lacks a unifying framework that both coherently integrates evolutionary accounts of aging and is directly useful for intervention assessment. Here, we propose the ‘Aging Onion’, a layered, two-axis framework developed to help interpret the diversity of phenotypes associated with aging, and informed by the mechanistic emphases foregrounded by the Disposable Soma and Hyperfunction traditions. In this framework, persistent activity of growth and developmental programmes, alongside insufficient somatic maintenance, define two broad biological axes through which we attempt to interpret age-related degeneration, and intervention responses. To examine the utility of this framework, we focus on nutrient sensing as an initial benchmark domain. Within this space, caloric restriction is a conserved reference intervention, while rapamycin provides a narrower pharmacological comparator acting primarily through TOR-centred signalling. We ask whether the proposed axes of the Aging Onion can help ground the mechanistic divergence between these interventions in aging-relevant biology and thereby interpret their differing efficacies. We conclude by outlining future directions for testing whether this framework can be operationalised in broader intervention assessment, and for determining whether its layered logic generalises beyond nutrient sensing to other domains of aging biology, including population-genetics approaches.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1726632</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1726632</link>
        <title><![CDATA[Acute changes in ankle dorsiflexor strength and fNIRS-Derived cortical activation following a single session of neuromuscular electrical stimulation in healthy older adults]]></title>
        <pubdate>2026-06-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yingqi Li</author><author>Luyi Wang</author><author>Congxiao Wang</author><author>Hujun Wang</author><author>Shaoting Zhang</author><author>Anda Xiu</author><author>Shengxuan Duan</author><author>Yingpeng Wang</author><author>Shuyan Qie</author>
        <description><![CDATA[BackgroundNeuromuscular electrical stimulation (NMES) is widely used to improve neuromuscular function, but most studies in healthy older adults have focused on longer-term outcomes such as muscle strength, mass, or architecture. Whether a single NMES session can induce measurable immediate changes in ankle-related neuromuscular performance and task-evoked cortical activity in healthy older adults remains unclear.MethodsTwenty-seven healthy older adults participated in this within-participant pre-post design study. A single 20-min NMES session was applied to the right tibialis anterior (40 Hz, maximum tolerable intensity, 2 s on/10 s off), with intensity individualized to maximal tolerable contraction (mean ± SD: 28.5 ± 6.2 mA; range: 18–42 mA). Before and after NMES, maximal ankle dorsiflexion performance was assessed on a dynamometer, and passive muscle biomechanical properties were quantified with MyotonPro. Whole-brain fNIRS was recorded during the dorsiflexion task. HbO signals were analyzed using a GLM with channel- and ROI-level inference, effect sizes, and false discovery rate (FDR) correction.ResultsNMES increased ankle dorsiflexion strength immediately after stimulation, whereas passive muscle mechanical properties showed no measurable short-term change. Task-related cortical activation was observed in both the pre-intervention and post-intervention sessions. Although exploratory analyses suggested some localized post-pre differences, no cortical effects survived correction for multiple comparisons. Exploratory brain-behavior correlations were observed, but none remained significant after correction.ConclusionA single session of NMES improved ankle dorsiflexion strength immediately in healthy older adults, while passive muscle mechanical properties did not change over the same period. Cortical activation was observed in both sessions, but no pre-post differences survived correction for multiple comparisons. The strength findings support an acute neuromuscular effect of NMES, whereas the cortical findings remain inconclusive.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1850676</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1850676</link>
        <title><![CDATA[Beyond chronological age: frailty, vitality, and subjective health structured by psychological segmentation in older adults]]></title>
        <pubdate>2026-06-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Eline Jasmijn Mertens</author><author>Damien S. E. Broekharst</author><author>Nathascha Hanzen</author><author>Karla de Rooij</author><author>Michel van Agthoven</author><author>Sjaak Bloem</author>
        <description><![CDATA[BackgroundChronological age remains a dominant factor in clinical decision-making despite its limited ability to reflect individual differences in functioning, vulnerability, and care needs. Age-based decision-making may contribute to exclusion from care and reinforce ageism. Psychological segmentation models, such as the Subjective Health Experience (SHE) model, classify individuals based on acceptance and perceived control of their health condition and have been proposed as a more individualized alternative. However, the relationship between SHE segments and established geriatric assessments such as frailty has not been examined.ObjectiveThis study examined how frailty, subjective health experience, and vitality relate to psychological profiles defined by the SHE model, and whether chronological age adds explanatory value beyond segmentation.MethodsA cross-sectional questionnaire study was conducted among community-dwelling Dutch adults aged ≥67 years (N = 753). Frailty was assessed using the Groningen Frailty Indicator (GFI), subjective health via a self-anchored ladder scale, and vitality via the Vita-16 instrument. Participants were classified into four SHE segments based on mean scores of ≥5.0 per dimension on acceptance and perceived control. Nonparametric analyses were used, with additional age-stratified comparisons (67–75 vs. ≥76 years).ResultsFrailty, subjective health, and vitality varied significantly across segments (all p < 0.001). Frailty prevalence ranged from 30% in segment 1%–74% in segment 4 (Cramer’s V = 0.41), with low acceptance emerging as the strongest differentiating factor. Segment 1 (high acceptance/high control) showed the most favorable outcomes; segment 4 (low acceptance/low control) showed the poorest. Frailty distinguished intermediate segments more clearly than vitality, with segment 3 (low acceptance/high control) showing higher frailty prevalence than segment 2 (69% vs. 40%). Chronological age did not differ across segments and did not moderate the association between segmentation and health outcomes, except for limited age effects on vitality in segments 1, 2, and 4.ConclusionPsychological segmentation via the SHE model explains meaningful variation in frailty, subjective health, and vitality in older adults, independent of chronological age. Frailty assessment combined with SHE segmentation enables a transition from age-based to needs-based care, supporting more tailored support strategies for older adults.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1816071</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1816071</link>
        <title><![CDATA[Senescent fibroblasts in aging and pulmonary fibrosis]]></title>
        <pubdate>2026-06-11T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Sara B. Palega</author><author>Aiwei Y. Borengasser</author><author>Yan Y. Sanders</author>
        <description><![CDATA[Aging is a major risk factor for many chronic lung diseases, including Idiopathic Pulmonary Fibrosis (IPF), a fatal and incurable disease characterized by progressive fibrotic remodeling. Age-associated structural alterations, impaired regenerative capacity, and dysregulated cellular signaling collectively create a pro-fibrotic microenvironment. A central driver of this pathological shift is the accumulation of senescent cells, which undergo irreversible growth arrest and develop a robust pro-inflammatory senescence-associated secretory phenotype (SASP). Emerging evidence identifies senescent lung fibroblasts as critical mediators of IPF pathogenesis. These cells promote excessive extracellular matrix deposition, myofibroblast differentiation, and tissue stiffening, while simultaneously impairing epithelial regeneration. Together, these effects create self-reinforcing feedback loops that perpetuate fibrotic remodeling and disease progression. To therapeutically target this process, strategies to use senolytics and senomorphics have been developed to eliminate senescent fibroblasts or attenuate their pathogenic secretory programs. However, significant translational challenges remain, including senescent cell heterogeneity, the lack of definitive and cell-specific biomarkers, and the need for targeted delivery approaches to enhance precision and minimize off-target effects. In this review, we delineate the mechanisms by which cellular senescence reprograms fibroblast function and disrupts normal lung repair to drive fibrosis, evaluate emerging therapeutic strategies, and discuss the key obstacles needed to be addressed to advance senescence-targeted interventions for IPF.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1805342</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1805342</link>
        <title><![CDATA[Case Report: Exceptional longevity in turner syndrome]]></title>
        <pubdate>2026-06-10T00:00:00Z</pubdate>
        <category>Case Report</category>
        <author>Mateus Vidigal de Castro</author><author>João Paulo Limongi França Guilherme</author><author>Mayana Zatz</author>
        <description><![CDATA[Turner Syndrome (TS), caused by complete or partial monosomy of chromosome X, is associated with increased morbidity and reduced life expectancy, largely driven by cardiovascular, endocrine, and metabolic complications. Here, we report the case of a 75-year-old woman with a confirmed diagnosis of non-mosaic TS (45,X) who remains clinically stable and functionally independent, beyond the expected survival for this condition. Notably, her mother is currently 101 years old, indicating a familial background of exceptional longevity. To explore the potential contribution of inherited genetic factors to this favorable phenotype, whole-genome sequencing (WGS) was performed in both the TS patient and her centenarian mother aiming to identify variants potentially associated with healthy aging and longevity. Hematological and biochemical analyses were subsequently used to functionally support the genetic and clinical findings, revealing preserved metabolic, inflammatory, and hematological profiles for the patient age. Together, these data suggest that a favorable genetic background may partially counterbalance the risks traditionally associated with X chromosome monosomy, contributing to preserved functional status into older age.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1819235</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1819235</link>
        <title><![CDATA[Efficacy of simultaneous aerobic and cognitive training (Activ4Brain) on physical fitness and body composition in older persons]]></title>
        <pubdate>2026-06-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Kaan Akalp</author><author>Hicran Besikci</author><author>Afonso Rainho Mateus</author><author>Luís Rama</author><author>José Pedro Ferreira</author><author>Maria José Ribeiro</author><author>Ana Maria Teixeira</author>
        <description><![CDATA[IntroductionThe popularity of simultaneously integrated cognitive training and exercise programs is increasingly adopted as a strategy to mitigate age-related declines in cognitive function and physical fitness, and these benefits may be further enhanced in a social context. However, the effects of integrated programs particularly when delivered as group activities on physical fitness and body composition have not been comprehensively investigated. Therefore, the purpose of this study is to evaluate and compare the effects of the Activ4Brain program on physical fitness and body composition with those of aerobic exercise alone.MethodsSeventy-four cognitively healthy older persons, with an average age of 65.5 ± 6.2 years, were assigned to control (n = 27) aerobic exercise (AE) (n = 23) and integrated cognitive and aerobic exercise (Activ4Brain) groups (n = 24). Physical fitness was assessed using a cardiopulmonary exercise test (CPET), timed up and go (TUG), 30 s chair stand, and hand grip strength tests. Body composition was assessed using bioimpedance (Inbody 770, Biospace). Evaluated parameters included body mass index (BMI), fat mass, fat percentage, muscle mass, fat to muscle ratio (FMR), and phase angle (PhA). Measurements were taken before and after the 24-session intervention period. Within-group comparison was done using paired t-test and Wilcoxon signed rank test. Between group comparison was done with one-way Anova or Kruskal Wallis tests by using mean differences for each group.ResultsPaired t-test results revealed significant increment in VO2 peak (p=.006), handgrip strength (p=.037), 30-s chair stand test (p=.004) for the AE group. Additionally, Paired t-tests results revealed a significant reduction in fat percentage (p=.019) and increment in hand grip strength (p = 0.019), 30-s chair stand test (p = 0.010), and PhA (p=.029) for the Activ4Brain group. Additionally, although no significant differences were observed in the within-group comparisons for the TUG test in any of the groups, the changes differed significantly between the control and aerobic exercise (AE) groups (p = .033), as indicated by the Kruskal–Wallis test.ConclusionBoth the AE and Activ4Brain interventions resulted in improvements in physical fitness suggesting that the inclusion of cognitive training in the Activ4Brain program did not compromise its ability to also improve physical function. Moreover, the Activ4Brain program also resulted in improvements in body composition by reducing fat percentage and increasing PhA. The Activ4Brain program was a useful strategy to improve physical fitness and maintain body composition in older persons, while also incorporating cognitive training.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1839323</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1839323</link>
        <title><![CDATA[Coronary angiography-derived microcirculatory resistance predicts adverse cardiovascular events in elderly with unstable angina post-percutaneous coronary intervention]]></title>
        <pubdate>2026-06-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Kangming Li</author><author>Lele Wang</author><author>Panqing Liao</author><author>Ya’nan Hu</author><author>Liming Xiong</author>
        <description><![CDATA[BackgroundCoronary microvascular dysfunction (CMD) has been increasingly recognized as a critical determinant of adverse cardiovascular outcomes. The coronary angiography-derived index of microcirculatory resistance (caIMR) has emerged as a promising noninvasive tool for CMD assessment, yet its prognostic value in elderly patients with unstable angina (UA) following percutaneous coronary intervention (PCI) remains insufficiently explored.MethodsThis single-center retrospective cohort study enrolled 348 elderly UA patients (age ≥65 years) who underwent PCI between June 2022 and February 2024. Patients were stratified by post-PCI caIMR using a cutoff value of 2.50 mmHg s/cm. The primary endpoint was major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure, angina rehospitalization, and cardiovascular death. Multivariable Cox regression and subgroup analyses were performed to evaluate the prognostic consistency of caIMR across different patient characteristics.ResultsPatients with caIMR ≥2.50 mmHg s/cm demonstrated significantly higher MACE rates. Multivariable analysis confirmed caIMR as an independent predictor, with diabetes mellitus also showing predictive value. Subgroup analyses revealed consistent prognostic value of caIMR regardless of hypertension status or diabetes.ConclusionNoninvasive caIMR assessment effectively stratifies post-PCI risk in elderly UA patients.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1769991</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1769991</link>
        <title><![CDATA[Gender- and domain-specific effects of a 6-month multidimensional exercise program on attention and verbal fluency in physically inactive older adults]]></title>
        <pubdate>2026-06-05T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Marlene Krumpolt</author><author>Anneke Schumacher</author><author>Lucas Sannemann</author><author>Kerstin Witte</author>
        <description><![CDATA[BackgroundRegular physical activity supports cognitive functioning in older age, yet little is known about domain- and gender-specific adaptations following multidimensional training. This study examined the effects of a six-month multidimensional exercise program on attention and verbal fluency in previously inactive older adults aged 65–70 years.MethodsParticipants were assigned to an intervention group (IG; n = 66, f = 44) or an inactive control group (CG; n = 31, f = 22). The six-month intervention combined structured fitness sessions and diverse recreational sports activities provided by local clubs, resulting in a multidimensional exercise program engaging physical, coordinative, cognitive, and social components. Selective and divided attention, reaction time, accuracy, and verbal fluency were assessed and analyzed using linear mixed models.ResultsSignificant improvements were observed for selective attention (Time × Group p = 0.034; Time × Group × Gender p = 0.031), with larger gains in men. Divided attention and phonemic fluency also improved, with women showing clearer benefits in divided attention and men in phonemic fluency. Semantic fluency remained largely stable at the group level, although within-group improvements were observed among women.ConclusionThe six-month multidimensional training program primarily reaches previously inactive older adults who would otherwise not find a suitable program and may support selective and divided attention as well as phonemic fluency. These findings highlight the relevance of gender-sensitive, multidimensional exercise interventions for maintaining cognitive functioning in later life.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1840035</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1840035</link>
        <title><![CDATA[Homeodynamic Rejuvenation: an adaptive framework for resetting skin aging]]></title>
        <pubdate>2026-06-03T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Anthony Brown</author><author>Carla Simonetto</author><author>Carlos López-Otín</author>
        <description><![CDATA[Skin aging reflects not only the accumulation of molecular damage, but also a progressive decline in the skin’s ability to restore equilibrium under continuous environmental stress. Classical models distinguishing intrinsic and extrinsic aging do not fully capture this dynamic process. In this article, we introduce Homeodynamic Rejuvenation as the restoration of functional competence and biological vitality, achieved not through reversal of visible signs of aging, but by re-establishing the skin’s ability to detect stress, coordinate adaptive responses, and recover efficiently following perturbation. Central to this framework is the concept of homeodynamic plasticity, which reflects the skin’s intrinsic capacity to dynamically sustain function under environmental and metabolic stress. By integrating principles of homeodynamics with exposome biology, this approach targets the reactivation of the cellular systems that govern stress sensing, repair, and recovery. Five core biological processes, namely, intracellular quality control, regenerative competence, metabolic resilience, cellular integrity, and structural integrity, underpin homeodynamic plasticity. Disruption or failure of one or more of these processes results in progressive functional decline, culminating in skin aging, of which dermatoporosis, a chronic cutaneous insufficiency syndrome, represents a terminal manifestation. These interconnected processes provide a coordinated basis for both restoring and assessing skin function. We propose that Homeodynamic Rejuvenation is best evaluated through dynamic perturbation–recovery kinetics, which quantify the skin’s ability to respond to and recover from stress. By linking these biological processes to measurable functional and clinical outcomes, Homeodynamic Rejuvenation offers a structured and translational framework for quantifying and restoring skin resilience.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1838730</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1838730</link>
        <title><![CDATA[The SIRT1–p53 axis drives a ferro-aging-like program and aggravates trophoblast dysfunction in preeclampsia]]></title>
        <pubdate>2026-06-03T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Rong Hu</author><author>Zhi Chen</author><author>Wei Bian</author><author>Jing Zhang</author><author>Xiaoqin Xu</author><author>Hui Xiong</author><author>Shaojian Xiang</author><author>Yubin Ding</author><author>Hongbo Qi</author><author>Huan Yang</author>
        <description><![CDATA[Preeclampsia (PE) is a pregnancy-specific syndrome driven by placental dysfunction, and premature placental senescence has increasingly been implicated in its pathogenesis. However, the upstream regulatory mechanisms remain poorly understood. Here, we found that placental SIRT1 expression was reduced in PE and was accompanied by senescence-associated features. In trophoblasts, SIRT1 knockdown enhanced senescence and senescence-associated secretory phenotype (SASP) release, while impairing proliferative capacity, migration, and invasion, whereas pharmacological activation of SIRT1 attenuated placental senescence and ameliorated PE-like manifestations in vivo. Mechanistically, iron chelation alleviated senescence, whereas senolytic intervention partially restored iron homeostasis, supporting a self-reinforcing interaction between iron dyshomeostasis and senescence. Collectively, these findings identify the SIRT1–p53 axis as an upstream regulator linking iron dyshomeostasis to placental senescence, support the existence of a ferro-aging-like pathogenic program in diseased placentas, and provide new insights into the molecular basis of placental dysfunction in PE.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1854915</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1854915</link>
        <title><![CDATA[The metabolic-epigenetic landscape of aging: interplay between histone acetylation, lactylation, and glycation]]></title>
        <pubdate>2026-06-03T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Olena Bolgova</author><author>Inna Shypilova</author><author>Volodymyr Mavrych</author>
        <description><![CDATA[BackgroundThe aging epigenome is shaped by three mechanistically distinct histone post-translational modifications—acetylation, lactylation, and glycation—each driven by a different metabolic flux: mitochondrial oxidative phosphorylation, glycolytic lactate production, and reactive carbonyl stress, respectively. Understanding their interplay is central to a molecular physiology of epigenetic aging.ScopeThis mini review synthesizes current evidence on the mechanisms of histone acetylation, lactylation, and glycation in aging; their crosstalk and convergence on shared regulatory nodes; and their modulation by environmental, nutritional, and behavioral factors. Key controversies and research gaps are critically appraised.Key FindingsNAD + decline in aging disables the sirtuin deacetylase family, dysregulating the histone acetylation landscape and impairing autophagy, mitochondrial biogenesis, and DNA repair. Histone lactylation, written by p300 at H3K18 and related lysine residues, is context-dependent: physiological pulses during exercise and sleep are adaptive, while chronic accumulation in diabetic microglia drives neuroinflammation via TLR4/NF-κB, and excess in tumor cells enables senescence bypass. Histone glycation by methylglyoxal irreversibly displaces regulatory marks and inactivates sirtuin proteins; pharmacological induction of glyoxalase I and glycation-lowering interventions reduce this burden and extend healthspan. These three axes may converge on a unified metabolic-epigenetic collapse that we propose constitutes the cellular basis of an ‘aging’ metabolic memory.Controversies and GapsLactylation erasers remain uncharacterized; the pro-versus anti-senescence duality of H3K18la is unresolved; and genome-wide histone glycation mapping in human tissues is absent.ConclusionCombinatorial interventions targeting NAD + restoration, modulation of lactylation, and reduction of carbonyl stress offer the most evidence-based approach to slowing metabolic-epigenetic aging.]]></description>
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