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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>2026-11-05T23:49:51.943+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1961490</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1961490</link>
        <title><![CDATA[Hyperbaric oxygen in cancer patients: a review of clinical safety, tissue selectivity, and therapeutic synergy]]></title>
        <pubdate>2026-11-05T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Avishai Abrahami</author><author>Shai Efrati</author>
        <description><![CDATA[BackgroundFor decades, the clinical application of Hyperbaric Oxygen Therapy (HBOT) in oncology has been constrained by theoretical concerns that hyperoxia might act as an unintended proliferative accelerator or tumor “fertilizer” by encouraging angiogenesis. This comprehensive review synthesizes the historical context, systematic review data, mechanistic literature, and clinical evidence to resolve three distinct questions: whether HBOT is safe in cancer patients, why its physiological effects diverge between healthy and malignant tissues, and how it can be leveraged synergistically with standard and novel oncological modalities.Safety FindingsThe human clinical record demonstrates a consistent, reproducible record of clinical safety across published cohorts. More than 38 independent human clinical reports published since 1970 have examined HBOT in cancer patients, and all found no association with tumor growth, recurrence, or metastasis. This consistency is reinforced by 19 randomized trials comprising 1,103 tumor-bearing patients prospectively evaluated under hyperoxia, none of which showed malignant acceleration at any site. A mathematical power analysis applied to this clinical corpus demonstrates that the probability of a genuine, undetected oncological hazard is less than 1×10−11.Tissue Selectivity and MechanismsThis safety profile rests on fundamental tissue selectivity. While intermittent hyperoxia drives tissue regeneration and upregulates antioxidant defenses in healthy host cells, malignant cells operating under the Warburg phenotype—characterized by severe mitochondrial structural degradation and cristolysis—possess a compressed redox margin. By reversing microenvironmental tumor hypoxia, hyperbaric oxygen destabilizes HIF-1alpha, suppresses glycolytic enzyme machinery, induces intrinsic mitochondrial apoptosis, and reverses epithelial-to-mesenchymal transition.Therapeutic SynergyBeyond clinical safety, hyperbaric hyperoxia acts as a potent therapeutic sensitizer. In randomized trials, adding HBOT to radiotherapy significantly reduced mortality and local recurrence in head and neck cancers. Mechanistically, HBOT dismantles dense extracellular matrix barriers, rebalances immunosuppressive myeloid components, and enhances T-cell infiltration, providing a clear rationale for combination with immunotherapies, chemotherapies, and ketogenic metabolic therapy.ConclusionActive or historical malignancy is not a valid contraindication for hyperbaric oxygen intervention. Hyperbaric oxygen functions as a tissue-selective biological signal—safe in healthy host tissue, disruptive to malignant survival architecture, and synergistic with modern oncological therapeutics.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1932016</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1932016</link>
        <title><![CDATA[Strengthening older adults’ healthcare reform in Nigeria through policy analysis and lessons from participatory health system innovations in Africa]]></title>
        <pubdate>2026-11-04T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Collins Chibueze Anokwuru</author><author>Moses Ifeatu Nwuzoh</author><author>Gabriel Chidera Edeh</author><author>Runyi Bassey Ogbet</author><author>Samson Adiaetok Udoewah</author><author>Chinemerem Victor Achor</author><author>Onyeka Chukwudalu Ekwebene</author><author>Stanley Eneh</author><author>Chidera Gabriel Obi</author><author>Francisca Onukansi</author><author>Ogechi Vinaprisca Ikhuoria</author><author>Chibueze Oluh</author><author>Gospel Chinaemerem Nwokocha</author><author>Ugonma Winnie Dozie</author><author>Uchechukwu Madukaku Chukwuocha</author>
        <description><![CDATA[Nigeria has expanded its policy architecture for ageing, yet older adults continue to face fragmented services, weak financial protection, limited age responsive care, and substantial barriers to healthcare access. This study examined why increasing policy recognition has not translated consistently into implementation and whether participatory health system innovations elsewhere in Africa offer relevant lessons for reform. A desk-based policy analysis was undertaken using Walt and Gilson’s Health Policy Triangle to examine the context, actors, content, and process shaping older adults’ healthcare in Nigeria. Purposively identified legislation, policy documents, institutional reports, and peer reviewed literature were interpreted deductively across the four HPT domains, with particular attention to five major national legislative and policy developments enacted or approved between 2004 and 2022. Comparative evidence from Zimbabwe’s Friendship Bench, South Africa’s older adult peer support model, Ghana’s Community Based Health Planning and Services programme, and Rwanda’s community health worker system was examined for potentially transferable principles rather than models for direct replication. The analysis identified an implementation gap arising from interacting constraints across all four policy domains. Demographic and epidemiological pressures are increasing within a resource constrained health system; institutional responsibilities remain fragmented; older adults and caregivers have limited influence in health governance; and broad policy commitments are not consistently matched by operational provisions for long term care, age responsive primary healthcare, workforce development, financing, monitoring, and accountability. The comparative cases highlighted potentially relevant principles including community participation, task sharing, peer support, integration with primary healthcare, structured supervision, and stronger referral pathways. However, the evidence base is heterogeneous: only some interventions were designed specifically for older adults, and differences in governance, financing, workforce capacity, and health system organisation constrain direct transferability. Strengthening older adults’ healthcare in Nigeria therefore requires greater attention to implementation rather than additional policy commitments alone. Reform should strengthen coordination, financial protection, age disaggregated monitoring, meaningful participation, and integration of community-based approaches within existing health system structures. Comparative innovations should be contextually adapted and evaluated through phased implementation before wider scale up.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1953389</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1953389</link>
        <title><![CDATA[Effect of papaverine hydrochloride on functional visual acuity in non-arteritic central retinal artery occlusion: a retrospective cohort study]]></title>
        <pubdate>2026-11-03T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Zhongzhong Liu</author><author>Qingli Lu</author><author>Tong Liu</author><author>Linna Peng</author><author>Yan Liu</author><author>Qiaoqiao Chang</author><author>Pei Liu</author><author>Mi Zhang</author><author>Chao Sun</author><author>Yan Huo</author><author>Na Zhang</author><author>Xuemei Lin</author><author>Shihui Wei</author><author>Songdi Wu</author>
        <description><![CDATA[BackgroundNon-arteritic central retinal artery occlusion (NA-CRAO) is an acute ocular emergency that frequently results in severe and irreversible vision loss with limited therapeutic options. Papaverine hydrochloride, a non-specific vasodilator commonly used to relieve vasospasm, has not been previously evaluated for its potential benefits for visual recovery in patients with NA-CRAO. Therefore, this study aims to investigate the association between papaverine hydrochloride treatment (PHt) and functional visual acuity improvement in patients with NA-CRAO.MethodsPropensity-score matching was used to retrospectively collect clinical data of 104 NA-CRAO patients with similar baseline characteristics. The patients were categorized into a PHt group (n = 52) and a non-papaverine hydrochloride treatment (non-PHt) group (n = 52). The primary outcome was functional visual acuity (best-corrected visual acuity ≥20/100) assessed at discharge and at a 1-month follow-up. Logistic regression and subgroup analyses were performed to evaluate the associations between papaverine hydrochloride use and improvements in functional visual acuity.ResultsThe PHt group showed significantly higher functional visual acuity than the non-PHt group at discharge (32.7% vs. 15.4%, p = 0.039) and at the 1-month follow-up (53.8% vs. 34.6%, p = 0.048). In adjusted models, treatment with papaverine hydrochloride was an independent favorable factor for improved functional visual acuity at discharge (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.20–10.36, p = 0.022) and at the 1-month follow-up (OR = 3.15, 95% CI: 1.19–8.29, p = 0.020). Subgroup analyses demonstrated consistent therapeutic effects across age, sex, the side of the affected eye, intra-arterial thrombolysis and intravenous thrombolysis strata, with no statistically significant interaction effects identified at either time point (all Pinteraction >0.05).ConclusionTreatment with papaverine hydrochloride was significantly associated with visual recovery in patients with NA-CRAO. Prospective further studies of causality are needed to validate these results and assess their safety.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1984937</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1984937</link>
        <title><![CDATA[Transcription–replication conflicts at telomeres: the emerging role of telomeric repeat-containing RNA (TERRA) R-loops in genome instability and cancer]]></title>
        <pubdate>2026-11-03T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Sibin Nambidi</author><author>Neeharika Sara Sennie</author><author>Sneha Pallatt</author><author>Antara Banerjee</author><author>Marco Scarpa</author><author>Surajit Pathak</author><author>Asim K. Duttaroy</author>
        <description><![CDATA[Telomeres are complex chromosomal components that are crucial for genome integrity but frequently experience replication stress due to their repetitive, G-rich nature and active transcription. TERRA is a mediator of telomere homeostasis but is also a causative factor of RNA-DNA hybrid (R-loop) formation, which can give rise to transcription-replication conflicts (TRCs). Telomeric R-loops that persist in the genome can act as a barrier to replication fork movement, cause reversal or collapse of replication forks, and result in fragile telomeres, break-induced replication, and telomere dysfunction. Although normal cells undergo senescence in response to this stress, cancer cells, especially those with alternative lengthening of telomeres (ALT), exploit telomeric TRCs to facilitate recombination-mediated telomere elongation.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.2034717</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.2034717</link>
        <title><![CDATA[Correction: Injuries among middle aged and older adult patients presenting to the emergency department: a retrospective cohort study]]></title>
        <pubdate>2026-10-30T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Abdullah M. Basnawi</author><author>Syeda Nafeesa Hashim</author><author>Sariya Khan</author><author>Husna Irfan Thalib</author><author>Ayesha Mirza Ayub</author><author>Sana Hashim</author><author>Fatimah Shakeel</author><author>Jumana Timraz</author><author>Fathma Islam</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1986107</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1986107</link>
        <title><![CDATA[Cellular senescence in skin inflammation: molecular mechanisms and potential clinical implications]]></title>
        <pubdate>2026-10-30T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Xinhe Wang</author><author>Beibei Xiong</author><author>Shuxiao Li</author><author>Yi Wang</author><author>Fulun Li</author>
        <description><![CDATA[Cellular senescence is increasingly regarded as a mechanism linking chronic tissue stress to persistent skin inflammation. Senescent cells are defined by stable cell-cycle arrest with remodeling of morphology, metabolism, and secretory phenotype, of which the senescence-associated secretory phenotype (SASP) is central. Because no single marker is sufficient, senescence in skin requires multiparameter, cell-type-resolved criteria. This Review addresses stress sensing, SASP induction, paracrine propagation, immune evasion, cellular heterogeneity, and therapeutic targeting, stratifying evidence by disease: chronic and diabetic wounds are best supported, whereas in psoriasis, atopic dermatitis, cutaneous lupus erythematosus, systemic sclerosis, and vitiligo the evidence remains largely associative, as SASP-like mediators overlap with cytokine programs from activated keratinocytes, stromal cells, and immune cells. Senescence-targeted interventions are classified as senolytics, senomorphics, or senopreventive/geroprotective strategies, and assessed at marker, SASP, senescent-cell-burden, and disease-outcome levels. It further notes that clinical translation depends on defining senescence-maintained lesion subtypes, establishing combinatorial biomarkers and spatial maps, and validating the efficacy and safety window of local therapies in suitable models and human tissues.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1933176</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1933176</link>
        <title><![CDATA[Sex-specific personality metatrait profiles and their associations with APOE, PICALM variants, and cognitive performance in healthy middle-aged adults: a cluster-based analysis]]></title>
        <pubdate>2026-10-29T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Adam Bednorz</author><author>Dorota Religa</author>
        <description><![CDATA[IntroductionAPOE ε4 is the strongest common genetic risk factor for late-onset Alzheimer’s disease, while PICALM rs3851179 has been associated with amyloid-β clearance. Personality can be summarized into two higher-order metatraits: Stability, reflecting emotional and behavioral regulation, and Plasticity, reflecting cognitive flexibility. This study examined whether genetic associations with episodic memory and fluid intelligence differ across Stability–Plasticity personality clusters in cognitively healthy middle-aged adults.Material and MethodsThe sample comprised 192 participants. NEO-FFI personality traits were standardized to derive the metatraits Stability and Plasticity. Sex-stratified agglomerative hierarchical clustering (Ward’s linkage) identified two personality profiles characterized by relatively higher or lower levels of both metatraits. Cognitive outcomes included the California Verbal Learning Test (CVLT) and Raven’s Progressive Matrices (RPM). Sex-stratified regression models examined associations between APOE ε4 carrier status, PICALM rs3851179 GG genotype, age, education, and cognitive performance.ResultsAfter false discovery rate correction, significant associations were observed only in females. In the low Stability–low Plasticity cluster, the APOE × age interaction was negatively associated with CVLT Recognition performance (pFDR = 0.019; R2 = 0.254). In the high Stability–high Plasticity cluster, models incorporating APOE and/or PICALM status were significantly associated with CVLT Recognition performance (R2 = 0.583–0.619, pFDR = 0.010–0.019). For fluid intelligence, significant negative APOE × age and APOE × age × education interactions, as well as a negative APOE × PICALM × age interaction, were observed in the respective models (R2 = 0.553–0.696, pFDR = 0.001–0.019).ConclusionPersonality metatraits were associated with variability in APOE-related cognitive outcomes, particularly among females. These findings suggest that personality structure can contribute to individual differences in cognitive aging pathways associated with genetic risk. However, the results should be interpreted considering the cross-sectional design and limited sample size.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.2029384</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.2029384</link>
        <title><![CDATA[Correction: New insight into Alzheimer’s disease: small molecule-Aβ in the brain transport and peripheral organ clearance]]></title>
        <pubdate>2026-10-29T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Tianci Ma</author><author>Yongyi Li</author><author>Yuting Ding</author><author>Shijie Liu</author><author>Chuanhao Gao</author><author>Xiang Li</author><author>Zhiqian Tong</author><author>Yan Lv</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1983741</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1983741</link>
        <title><![CDATA[Sociodemographic patterns of psychological distress, non-communicable diseases, and disability among south Africans 60 years and older: a generalized structural equation modelling approach]]></title>
        <pubdate>2026-10-29T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Sbonelo Chamane</author><author>Simangaliso Mnyandu</author><author>Lehlogonolo Makola</author><author>Musawenkosi Mabaso</author><author>Zaynab Essack</author><author>Ronel Sewpaul</author><author>Sean Jooste</author><author>Sizulu Moyo</author><author>Nompumelelo Zungu</author><author>Khangelani Zuma</author>
        <description><![CDATA[BackgroundSouth Africa is experiencing a steady increase in ageing population alongside a growing burden of non-communicable diseases (NCDs), disability and mental health challenges. However, the interplay between these conditions in later life remains underexplored.MethodsThe study draws data from the sixth South African National HIV Prevalence, Incidence and Behaviour Survey which used a multi-stage, stratified, cluster random sampling design. The analysis estimated the prevalence of self-reported psychological distress, NCDs and disability among adults aged 60 years and older. Sociodemographic factors associated with these outcomes were examined using a Generalized Structural Equation Model.ResultsAmong adults aged 60 years and older, the prevalence of psychological distress was 3.1%, NCDs 59.7%, and disability 64.1%. Having at least one NCD significantly increased the likelihood of psychological distress, while having a disability increased the likelihood of having an NCD. Women and those aged 70–79 years had higher odds of both NCDs, and disability compared to men and those aged 60–69 years, respectively. Compared to Black Africans, participants from other racial groups had lower odds of distress but higher odds of NCDs. Relative to primary education, secondary education lowered the odds of distress and disability but increased the odds of NCD, while tertiary education was only protective against disability. Unemployment was associated with higher odds of NCDs, while residing in rural informal areas and never being married was associated with lower odds of NCDs only, compared to those who were employed, living in urban areas and ever married, respectively.ConclusionThe findings highlight strong interconnections between chronic disease, disability and mental health in later life, shaped by age, sex, education, marital status and place of residence. Interventions that integrate social, physical and psychological care are essential to improving healthy ageing outcomes in South Africa.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1986986</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1986986</link>
        <title><![CDATA[Aging remodels progenitor and niche interactions in lung regeneration]]></title>
        <pubdate>2026-10-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Fernanda Toscano-Marquez</author><author>Angeles Garcia-Vicente</author><author>Uriel Camacho-Silverio</author><author>Tania Valdivia-Herrera</author><author>Mariana Río de la Loza</author><author>Elisa Hernández-Xóchihua</author><author>Remedios Ramírez</author><author>Moises Selman</author><author>Annie Pardo</author><author>Yair Romero</author>
        <description><![CDATA[IntroductionProgenitor cells in aged tissues undergo changes in their microenvironment that may impact their functionality during regeneration. Despite recent advances in understanding the role of adult lung progenitors, the impact of aging on these cells remains unclear.MethodsTo analyze aging modifications, we used aged wild-type mice of 18–24 months old, and Zmpste24–/– deficient mice, which exhibit an accelerated phenotype. A three-dimensional organoid culture system was employed to assess in vitro regenerative capacity. Additionally, cells were isolated and characterized with senescence and autophagy markers.ResultsOur findings revealed that lung epithelial cells from aged mice and Zmpste24–/– mice retain organoid forming potential, maintaining their phenotype and cellular homeostasis through increased autophagy-associated transcriptional response, particularly when co-cultured with young fibroblasts. Moreover, these progenitor cells may exhibit increased susceptibility to mechanical stress with aging potentially associated with reduced nuclear lamins and the Zmpste24 defect. This vulnerability is illustrated by FACS sorting, which can further compromise their regenerative potential. By contrast, cultured fibroblasts from Zmpste24–/– mice show nuclear defects and acquire a senescent phenotype, characterized by the mechanistic target of rapamycin complex 1 (mTORC1) activation and reduced autophagy, which in turn impairs organoid formation.DiscussionOur results indicate that, in aging, progenitor cells and their fibroblast niche integrate microenvironmental signals that shape cell-cell interactions essential for lung regeneration.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1887671</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1887671</link>
        <title><![CDATA[Maternal age-related thyroid changes during pregnancy: implications for isolated hypothyroxinemia patterns]]></title>
        <pubdate>2026-10-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Saifeng Wang</author><author>Yili Zhang</author><author>Ailin Zhu</author><author>Yu Meng</author>
        <description><![CDATA[ObjectiveTo investigate the associations between maternal age and thyroid function in early and late pregnancy, as well as their changes, with a focus on the impact of age on the longitudinal patterns of isolated hypothyroxinemia.MethodsThis retrospective cohort study included 43,545 women with singleton pregnancies. Serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured in early and late pregnancy, along with their changes. Linear regression, restricted cubic spline (RCS), and piecewise linear regression were used to assess non-linear associations and threshold effects. Isolated hypothyroxinemia was categorized into euthyroid, transient, and persistent patterns. Ordinal logistic regression was used to examine the association between maternal age and these patterns, as well as the relationships between the patterns and adverse pregnancy outcomes, including preeclampsia, preterm birth, macrosomia, and low birth weight (LBW).ResultsMaternal age showed significantly stronger negative associations with FT4 levels and their changes than with TSH. Maternal age was positively associated with the risk of isolated hypothyroxinemia in a dose–response manner. Compared with women aged 18–24 years, those aged 35–39 years (OR = 1.89) and 40–49 years (OR = 3.01) had higher risks of persistent isolated hypothyroxinemia. Risks of preeclampsia, macrosomia, and LBW increased progressively from transient to persistent patterns (all P for trend <0.01).ConclusionMaternal age is an important factor influencing FT4 during pregnancy. Increasing age is associated with a higher likelihood of persistent isolated hypothyroxinemia, which is linked to a broader range of adverse pregnancy outcomes.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1939566</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1939566</link>
        <title><![CDATA[Triterpenoids – future multi-target compounds against obesity and towards restoration of metabolic health]]></title>
        <pubdate>2026-10-27T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Johanna Becker</author><author>Birgitta E. Ebert</author><author>Gunter Festel</author><author>Lars M. Blank</author>
        <description><![CDATA[Obesity and its associated diseases represent one of the most urgent public health crises of our time, affecting billions worldwide. Current pharmacological agents, such as GLP-1 and GLP-1/GIP receptor agonists, have demonstrated high clinical efficacy in diabetes and weight management. However, the required lifelong medication is often limited by high economic costs and severe side effects, including gastrointestinal complications. Consequently, the search for complementary therapies is invaluable. This review highlights the potential of natural triterpenoids in obesity management by shifting the focus towards long-term metabolic restoration. Triterpenoids can serve as multi-target agents that address key pathways, such as AMPK and Akt/mTOR, thereby positively regulating autophagy processes and improving metabolic imbalances. Celastrol, for example, acts as a leptin sensitizer, restoring satiety signaling; ursolic acid drives body recomposition by enhancing energy expenditure; and ginsenosides modulate multiple processes, including browning, adipogenesis, lipogenesis, and satiety signaling. Furthermore, oleanolic acid promotes pathways associated with cellular healthspan by activating telomerase, while betulinic acid suppresses de novo fatty acid synthesis independently of food intake. However, low oral bioavailability remains the major challenge to successfully translating these findings from animal models to clinical applications. Advanced strategies, such as sustainable bioproduction via genetically modified microorganisms, engineered probiotics, or nanotechnology-based delivery systems, offer promising opportunities to overcome these pharmacokinetic and safety limitations. Addressing these barriers is essential to translate triterpenoids into therapeutic agents for human metabolic health and healthy aging.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.2008892</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.2008892</link>
        <title><![CDATA[Epigenetic aging in the tumor microenvironment: mechanisms and implications for immunotherapy]]></title>
        <pubdate>2026-10-27T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Fusako Takezawa</author><author>Yohei Sato</author>
        <description><![CDATA[Aging reshapes the tumor microenvironment (TME) by altering the immune, stromal, and vascular compartments, yet these changes are not fully explained by chronological age. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA programs, may contribute to persistent alterations in cellular function and communication. In this review, we synthesize current evidence on epigenetic remodeling in the aged TME, distinguishing established findings in aging and cancer from mechanisms that remain to be demonstrated specifically in aged tumors. We highlight how epigenetic changes intersect with cellular senescence, chronic inflammation, and metabolic stress to weaken antitumor immunity and influence treatment response, with particular attention to T-cell dysfunction, regulatory T-cells, myeloid cells, fibroblasts, and endothelial cells. We also discuss the limitations of bulk-tissue epigenetic clocks and the emerging value of cell-resolved and spatial analyses. Finally, we consider therapeutic implications, including epigenetic therapies, senescence-directed interventions, and selective targeting of suppressive immune-stromal interactions, while noting that their ability to reverse TME aging remains uncertain. Integrating longitudinal human studies with functional experiments will be essential to determine whether epigenetically altered immune-stromal niches can serve as biomarkers or therapeutic targets beyond chronological age alone.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1913194</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1913194</link>
        <title><![CDATA[Maintaining Klotho: preventing the body from unwinding]]></title>
        <pubdate>2026-10-27T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Walter H. Gunzburg</author><author>Pharon Pawa</author><author>Brian Salmons</author>
        <description><![CDATA[The Klotho gene, discovered in 1997, encodes a protein that plays a pivotal role in regulating aging and longevity. Reduced Klotho expression is associated with multiple age-related diseases, including renal, cardiovascular, neurodegenerative, and metabolic disorders, leading to the notion that supplementation of the levels of Klotho may have a beneficial, or even a therapeutic, effect. Despite promising early stage results from recombinant and gene-based therapies, clinical translation has been hindered in part by the protein’s short half-life as well as the immune clearance of Klotho producing cells. This article reviews Klotho’s biological significance and therapeutic challenges, as well as introducing a novel encapsulation-based approach—Cell-in-a-Box® technology—as a proposed potential solution for sustained Klotho delivery. Encapsulated Klotho-producing cells may potentially enable continuous secretion, immune protection, and long-term efficacy, offering a transformative strategy for anti-aging and disease modification.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1868924</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1868924</link>
        <title><![CDATA[Functional status following the COVID-19 lockdown and five-year survival among older adults with pre-existing functional dependence: a cohort study]]></title>
        <pubdate>2026-10-22T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Vicente Martín Moreno</author><author>Asunción García Mateos</author><author>Amanda Martín Fernández</author><author>Laura Flórez Busto</author><author>Beatriz Alonso Serna</author><author>Annly Luzmila Vásquez Alay</author><author>María del Carmen Cubero Sobrados</author><author>Jorge Hurtado Gallar</author><author>Juana Marcos Guerra</author><author>María Inmaculada Martínez Sanz</author><author>Irene Sánchez González</author><author>Elena Sánchez Rodríguez</author><author>Miriam Fernández Gallardo</author><author>Elena Pérez Rico</author>
        <description><![CDATA[IntroductionLockdown for the COVID-19 pandemic in Spain (14 March 2020 - 21 June 2020) represented a situation of prolonged stress; this study analyzed the association between changes in functional status observed after the lockdown and 5-year survival.Materials and MethodsA prospective longitudinal cohort study conducted between 22 June 2020, and 30 June 2025. As of 1 March 2020, Orcasitas (Madrid, Spain) had 150 residents with functional dependence. Four people died during the lockdown. Another 19 were excluded, leaving a final sample of 127 participants. Pre- and post-lockdown functional trajectories were analyzed in relation to the ability to perform basic (ADLs) and instrumental (IADLs) activities of daily living.ResultsAfter lockdown for the COVID-19 pandemic, 62.2% of these individuals improved their functional capacity; 50.6% did so to a clinically significant degree (25–75 points); and 43.3% stopped meeting criteria for functional dependence according local protocol (Barthel>60). This improvement was associated with less dependence on performing ADLs and IADLs. At the 3-year follow-up, 50% maintained a better score compared to their pre-lockdown Barthel Index, but only 22.2% did so compared to their post-lockdown Barthel Index. A lower Barthel Index score before and after lockdown was associated with a lower probability of survival at 5 years. Maintaining functional dependence (Barthel≤60) after the lockdown was also associated with a higher risk of mortality (HR 2.130; CI 1.322–3.434). Age, having no formal education, living with children, being unable to leave the house independently, and being unable to shop on one’s own, were associated with a lower probability of survival.ConclusionFunctional trajectories observed after lockdown in this cohort showed that the outcome associated with survival was not the improvement in functional capacity or the intensity of that improvement, but rather exceeding the 60-point threshold on the Barthel Index. In this cohort, a combined analysis of ADLs and IADLs might better reflect the potential capacity to make these changes than an analysis of the Barthel Index alone. The observed functional trajectories suggest as an exploratory hypothesis of a latent intrinsic capacity, construct that would encompass functional reserves not routinely utilized in daily life.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1869552</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1869552</link>
        <title><![CDATA[Impact of habitual physical activity and age on T cell metabolism and activation via β2-adrenergic receptor modulation]]></title>
        <pubdate>2026-10-20T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Amanda V. Sardeli</author><author>Ana Ramkrapes</author><author>Jakob Boyes-Jensen</author><author>Jon Hazeldine</author><author>Helena Batatinha</author><author>Niharika A. Duggal</author><author>Davide Calebiro</author><author>James E. Turner</author>
        <description><![CDATA[BackgroundAgeing impairs T cell function and responses to vaccines and infections. Effective T cell function requires rapid metabolic switching towards glycolysis, which becomes dysregulated with age. We have shown that physically active older adults have T cells that are more functional and metabolically fit. As exercise acutely elevates adrenaline and mobilises T cells via β2-adrenergic receptors (β2-AR), we hypothesise that habitual physical activity (PA) preserves β2-AR-mediated metabolic stimulation in T cells from older adults.MethodsOlder adults (≥65 years) with habitually high PA (HPA, n = 6) or habitually moderate PA (MPA, n = 6) were compared with young controls (18–35 years, n = 6). T cells were exposed to the β-agonist isoproterenol for 30 min to mimic acute exercise-like adrenergic stimulation, with or without the β2-AR blocker ICI-118,551. Following 1 h of rest, T cells were stimulated for 4 h in vitro with PMA and ionomycin. T cell activation (CD69), glucose transporter-1 (Glut1), intracellular cAMP concentrations under isoproterenol stimulation, and β2-AR mRNA expression were assessed.ResultsOlder adults exhibited impaired CD8+ T cell activation and β2-AR blockade inhibited activation in all groups. Glut1 expression in CD8+ T cells was higher in older MPA than young, but did not differ from older HPA. In CD8+ T cells that were not stimulated with PMA and ionomycin, β2-AR blockade (with β-AR stimulation) increased Glut1 expression in all groups compared with β-AR stimulation alone, and this increase was greater in older HPA than MPA (p = 0.043). No group differences were observed in β2-AR mRNA expression or isoproterenol-induced β-AR cAMP responsiveness.ConclusionThese exploratory findings indicate that individuals with higher levels of habitual PA have lower age-associated impairments in CD8+ T cell activation and metabolic switching in response to β stimulation. Interestingly, β2-AR blockade did not fully abrogate β stimulation, therefore future studies should investigate a potential influence of β1-AR in this modulation, to generate definitive conclusions.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.2016735</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.2016735</link>
        <title><![CDATA[Correction: Bone mineral density and turnover response to GLP-1 receptor agonists in older adults with overweight/obesity and prediabetes/type 2 diabetes: a 20-week pilot trial post hoc analysis]]></title>
        <pubdate>2026-10-19T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Lauren Dinkla</author><author>Kristen M. Beavers</author><author>Ronna Robbins</author><author>Dela Akpalu</author><author>Sarah J. Wherry</author><author>Gary Miller</author><author>Daniel P. Beavers</author><author>Sara Espinoza</author><author>Jonathan Trejo</author><author>Allison Stepanenko</author><author>Tiffany M. Cortes</author>
        <description></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1963384</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1963384</link>
        <title><![CDATA[Longitudinal immune trajectories following SARS-CoV-2 vaccination in long-term care facility residents: an unsupervised analysis approach]]></title>
        <pubdate>2026-10-19T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Annapina Palmieri</author><author>Cecilia Damiano</author><author>Pasqualina Leone</author><author>Caterina Trevisan</author><author>Alba Malara</author><author>Alberto Zucchelli</author><author>Raffaele Antonelli Incalzi</author><author>Rosa Prato</author><author>Francesca Fortunato</author><author>Tatjana Baldovin</author><author>Alessandra Coin</author><author>Pasquale Minchella</author><author>Stefania Giordano</author><author>Anna Teresa Palamara</author><author>Graziano Onder</author><author>Giorgio Fedele</author>
        <description><![CDATA[BackgroundResidents of Long-Term Care Facilities (LTCFs) represent a highly vulnerable population characterized by immunosenescence, multimorbidity, and heterogeneous immune responses to repeated SARS-CoV-2 vaccination and infection. Conventional analyses based on single clinical variables often fail to capture this complexity. We evaluated longitudinal humoral immune responses in institutionalized older adults to identify data-driven antibody profiles and characterize cluster-specific waning kinetics.MethodsIn a prospective multicenter cohort of 388 Italian LTCF residents followed across four time points (T0–T3 over 12 months), longitudinal anti-Spike (anti-S) and anti-Nucleocapsid (anti-N) IgG levels were measured alongside demographic and vaccination data. Principal Component Analysis (PCA) was used for dimensionality reduction, followed by K-means clustering. Optimal cluster number was determined using internal validation metrics (Silhouette, Calinski-Harabasz, and Davies-Bouldin indices) and bootstrap stability analysis. Linear mixed-effects models were applied to describe cluster-specific antibody waning trajectories.ResultsA longitudinal analysis was conducted on 388 LTCF residents. Three antibody trajectory profiles emerged: (i) a Vaccine-Driven profile (n = 130), characterized by moderate anti-S titers and progressive antibody decline; (ii) a Hybrid Immunity profile (n = 125), characterized by evidence of prior infection and remarkably stable antibody concentrations throughout follow-up despite limited uptake of the 2023/2024 booster; and (iii) a High-Peak Hybrid Responder profile (n = 133), exhibiting the highest baseline anti-S titers followed by the steepest rate of antibody waning. Across the cohort, 12 of 388 residents (3.1%) developed documented symptomatic SARS-CoV-2 infection during follow-up, with no COVID-19-related deaths and no significant difference in infection incidence among profiles. Bootstrap stability analysis showed a mean Adjusted Rand Index (ARI) of 0.74 (SD 0.20).ConclusionUnsupervised machine learning effectively resolves the complex heterogeneity of SARS-CoV-2 humoral responses in LTCF residents into data-driven trajectory patterns. These findings illustrate the utility of data-driven approach for describing humoral dynamics while distinguishing observational antibody kinetics from direct estimates of clinical protection.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1965961</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1965961</link>
        <title><![CDATA[Percentile model and usual gait speed reference values in Colombian older adults: a secondary analysis of the Survey on Health, Wellbeing, and Aging in Latin America and the Caribbean (SABE)]]></title>
        <pubdate>2026-10-19T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Philippe Tadger-Viloria</author><author>Margareth Lorena Alfonso-Mora</author><author>Diana Díaz-Vidal</author><author>Aura Cristina Quino-Ávila</author><author>John Andrew</author><author>Carolina Sandoval-Cuellar</author><author>Eliana Monsalve-Jaramillo</author><author>Maria Giné-Garriga</author>
        <description><![CDATA[IntroductionGait speed is a simple and clinically relevant indicator of physical function in older adults; however, population-specific reference values are needed for its interpretation. This study aimed to establish reference values and a percentile model for usual gait speed among community-dwelling Colombian older adults and to examine factors associated with slow gait speed.MethodsData from 11,945 community-dwelling older adults participating in the Survey on Health, Wellbeing, and Aging in Latin America and the Caribbean (SABE) were analyzed. Slow gait speed was defined as <0.8 m/s. Univariate associations between gait speed and age, sex, height, calf circumference, waist circumference, and urban/rural residence were examined. Reference percentiles for gait speed were modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS), incorporating age, sex, height, calf circumference, waist circumference, and body mass index. Model selection was guided by Q statistics and the Generalized Akaike Information Criterion (GAIC).ResultsGait speed ranged from 0.6 to 1.4 m/s, with a mean of 0.79 m/s and a median of 0.76 m/s. Slow gait speed was more frequent among female than male participants (56% of those with slow gait speed were female). Participants with slow gait speed were older than those without slow gait speed (69.21 vs. 67.53 years). Slow gait speed was significantly associated with older age, female sex, shorter height, lower calf circumference, higher waist circumference, and rural residence. Height accounted for a substantial proportion of the sex-related differences in gait speed, particularly among the oldest participants.DiscussionThis study provides population-specific reference values and percentile estimates for usual gait speed among community-dwelling Colombian older adults. The findings highlight the importance of considering anthropometric characteristics, particularly height, when interpreting sex-related differences in gait speed. These normative values may facilitate the clinical interpretation of gait speed and support assessment and intervention planning in the Colombian older population]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1971981</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1971981</link>
        <title><![CDATA[Impaired autophagy and lysosome function in human fibroblast aging]]></title>
        <pubdate>2026-10-14T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Juan José Unzueta-Mendoza</author><author>Ian García-Aguirre</author><author>Mina Königsberg</author><author>Isabel Arrieta-Cruz</author><author>Solangy Lizcano-Meneses</author><author>Jonathan J. Magaña</author><author>Adriana Alarcón-Aguilar</author><author>Bulmaro Cisneros</author>
        <description><![CDATA[BackgroundHuman aging is characterized by a progressive, time-dependent deterioration in physiological and cognitive functioning. Aging is driven by an array of interconnected cellular hallmarks, including genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alteration and dysfunctional autophagy. Autophagy is a cytoprotective (cellular degradation and recycling) pathway that maintains homeostasis during starvation or stress, and whose activity is associated with extended lifespan. This multi-step process comprises autophagosome formation and maturation, autophagosome–lysosome fusion, and cargo degradation. Thus, analysis of autophagy flux is necessary to precisely design therapeutic interventions aimed at restoring autophagy in aging.MethodsThe autophagy flux was comprehensively analyzed in human skin fibroblasts from donors of different ages (20–96 years old), a cell system that retains age-associated cellular and molecular signatures. The subcellular localization and activity of the master transcription factor of autophagy and lysosome biogenesis, TFEB, was analyzed by confocal microscopy assays and transcriptional expression of TFEB target genes (RT-qPCR) respectively. The autophagy flux was evaluated by monitoring the autophagy markers LC3 and p62 by Western blotting and confocal microscopy analyses, using inhibitor drugs to block autophagy or lysosomal activity. Autophagosome maturation and autophagosome-lysosome fusion were analyzed by colocalizing LC3 with Sintaxin-17 and LC3 with the lysosomal protein LAMP1 respectively, using inhibitor drugs and confocal microscopy assays. The analysis of lysosomal morphology and function was evaluated by lysobrite dye staining and live-cell confocal microscopy analysis.ResultsThe initial stages of autophagy, including activation of TFEB, and autophagosome formation, remained apparently functional in fibroblast aging. In contrast, the rate of both autophagosome maturation and autophagosome-lysosome fusion, as well as the lysosomal function appears to be altered in aged fibroblasts. Specifically, enlarged dysfunctional lysosomes were identified as a hallmark of the fibroblasts of the 96-year-old donor. This lysosomal dysfunction may lead to a reduced ability to degrade canonical autophagy markers, LC3-II and p62, and the accumulation of lipofuscin.ConclusionOverall, the results provide evidence that autophagy flux is impaired at the late stages in aged fibroblasts, specifically in autophagosome maturation and autophagosome-lysosome fusion steps. Furthermore, it was demonstrated that this failure correlates with the presence of enlarged dysfunctional lysosomes. This study underscores the significance of enhancing lysosomal activity to counteract autophagy decline in aging.]]></description>
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