Frontiers in aging最新文献

{"title":"Age-related hearing loss persisted in mice that had demonstrated improved healthspan, reduced inflammaging and extended lifespan following expression of the naked mole-rat transgene for hyaluronan synthase 2.","authors":"Connor E Owens, Aiden J Borruso, Kevin A Place, Andrei Seluanov, Vera Gorbunova, Patricia M White, Ned J Place","doi":"10.3389/fragi.2026.1936677","DOIUrl":"10.3389/fragi.2026.1936677","url":null,"abstract":"<p><strong>Background: </strong>Approximately one in three adults aged 65-74 years reports hearing difficulty, including age-related hearing loss (AHL, presbycusis). The C57BL/6 mouse is widely used in preclinical AHL research because it develops AHL relatively early. Calorie restriction (CR) attenuates AHL and improves healthspan and longevity in this strain. A recently developed transgenic C57BL/6 mouse expressing naked mole-rat hyaluronan synthase 2 (<i>nmrHas2</i>), which produces very high molecular mass hyaluronan (vHMM-HA), also exhibits improved healthspan, reduced inflammaging, and increased longevity. Therefore, we evaluated <i>nmrHas2</i> mice for evidence of alleviated AHL.</p><p><strong>Objective: </strong>To determine whether AHL is attenuated in <i>nmrHas2 mice</i>.</p><p><strong>Methods: </strong>This study supplemented a larger investigation of <i>nmrHas2</i> and female reproductive aging. Tamoxifen administered at 1 month induced ubiquitous <i>nmrHas2</i> expression in <i>nmrHas2+</i> females; <i>nmrHas2-</i> controls received tamoxifen or vehicle. Auditory brainstem response (ABR) testing was performed approximately 2 weeks before mice reached 3 or 12 months of age. Cochleae and reproductive tissues were collected following euthanasia approximately 2 weeks later.</p><p><strong>Results: </strong>ABR thresholds to clicks and six tones (4-32 kHz) showed marked hearing loss from 3 to 12 months of age in both <i>nmrHas2+</i> mice and controls, with no evidence that <i>nmrHas2</i> attenuated AHL. Cochlear <i>nmrHas2</i> expression in <i>nmrHas2+</i> mice was confirmed by quantitative RT-PCR.</p><p><strong>Conclusion: </strong>Ubiquitous <i>nmrHas2</i> expression did not attenuate AHL in C57BL/6 mice despite previously reported benefits for other aging phenotypes. These findings contrast with CR, suggesting that vHMM-HA and CR influence aging through distinct mechanisms.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1936677"},"PeriodicalIF":4.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing MK0873 as a non-covalent hTERT-Targeting compound: a proof of concept study.","authors":"Maham Ansari, Abdul Wali, Mohhamed Rasul, Kristina Gemzell Danielsson, Twana Alkasalias, Muhammad Mushtaq","doi":"10.3389/fragi.2026.1783019","DOIUrl":"10.3389/fragi.2026.1783019","url":null,"abstract":"<p><p>Telomerase is a key regulator of both cellular immortality and aging, making it an attractive target for cancer therapy and age associated pathologies. Its clinical exploitation has been limited by structural complexity and challenges in achieving specificity. Recent structural insights into human telomerase reverse transcriptase (hTERT) have enabled the identification of selective inhibitors. Here, we repurposed MK0873, a PDE4 inhibitor previously evaluated in Phase II clinical trials for rheumatoid arthritis and COPD, as a non covalent telomerase targeting agent. <i>In silico</i> docking and molecular dynamics simulations predicted stable binding of MK0873 to hTERT, distinct from the covalent interaction of BIBR1532. Analysis of neuroblastoma datasets revealed that high TERT expression correlates with poorer survival, independent of MYCN amplification. MK0873 reduced proliferation of hTERT positive cells, promoted cellular senescence and decreased relative telomere length, whereas ALT positive cells exhibited minimal response, supporting selective activity in telomerase dependent cellular models. Importantly, direct biochemical assessment using the Telomeric Repeat Amplification Protocol assay demonstrated a significant reduction in telomerase activity following MK0873 treatment, providing experimental evidence that complements the computational predictions and cellular phenotypes observed in this study. Although the magnitude of telomerase inhibition was lower than that of the reference inhibitor BIBR1532 under identical experimental conditions, the combined computational, biochemical and cellular findings consistently support hTERT as a relevant molecular target of MK0873. Collectively, these results provide proof of concept evidence that MK0873 represents a promising lead scaffold for non covalent targeting of hTERT. While additional studies are required to further define cellular target engagement, distinguish potential PDE4 dependent effects and optimize inhibitory potency. Current work establishes a foundation for the continued development of MK0873 derived compounds as potential telomerase targeted anticancer therapeutics.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1783019"},"PeriodicalIF":4.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of sarcopenia and paraspinal muscle morphology on conservative treatment outcomes in lumbar spinal stenosis: a prospective cohort study.","authors":"Zhangmeng Xu, Tao Xu, Jing Guo, Jinshun Zou, Jiajia Luo, Fan Chen, Xin Zhang, Ji Wu","doi":"10.3389/fragi.2026.1913710","DOIUrl":"10.3389/fragi.2026.1913710","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of sarcopenia on postoperative outcomes in lumbar spinal stenosis (LSS) is well documented, but its role in conservative treatment remains unclear. In this prospective cohort study, we examined the association between sarcopenia and outcomes after conservative treatment in elderly LSS patients and explored whether paraspinal cross-sectional area (CSA) and fat percentage mediate this relationship.</p><p><strong>Methods: </strong>Elderly LSS patients undergoing conservative treatment at Sichuan Provincial Orthopedic Hospital (June 2023-May 2025) were enrolled. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia. The primary outcome was >50% improvement in the Japanese Orthopedic Association (JOA) score at discharge. Missing data were imputed with random forest. Candidate predictors were screened using univariate logistic regression (<i>p</i> < 0.1) and selected using the least absolute shrinkage and selection operator (LASSO) regression. Sensitivity analyses comprised Firth's penalized correction for sparse data, subgroup analyses, and examination of individual sarcopenia components [appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed] in relation to treatment outcome. Mediation analysis with bootstrap resampling evaluated total paraspinal CSA and mean fat percentage as mediators.</p><p><strong>Results: </strong>Among 463 patients, 89 (19.2%) had sarcopenia. Sarcopenic patients had significantly smaller paraspinal CSA and greater fat infiltration than non-sarcopenic patients. After adjustment for sex, age, and albumin, sarcopenia remained independently associated with poor discharge outcome (OR = 0.21, 95% CI: 0.12-0.38, <i>p</i> < 0.001). Subgroup analyses showed consistent effects across age, sex, body mass index (BMI), albumin, and stenosis severity strata (all <i>p</i> for interaction >0.05). Among individual components, ASMI and grip strength independently predicted poor outcomes, whereas gait speed did not. Mediation analysis demonstrated that total paraspinal CSA mediated 74.64% of the effect (<i>p</i> = 0.012), whereas mean fat percentage showed no significant mediation (<i>p</i> = 0.710). Sensitivity analyses confirmed the robustness of these findings against missing data, model specification, and sparse data bias.</p><p><strong>Conclusion: </strong>Sarcopenia is independently associated with worse short-term outcomes after conservative treatment in older LSS patients, with this association statistically mediated by reduced paraspinal CSA.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1913710"},"PeriodicalIF":4.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive immune cells and kidney function in older adults: sex-specific associations in the health and retirement study (HRS).","authors":"Shannon M Sullivan, Bibin Joseph, Shweta Sharma, Weihua Guan, Amy B Karger, Jessica Faul, Bharat Thyagarajan","doi":"10.3389/fragi.2026.1882462","DOIUrl":"10.3389/fragi.2026.1882462","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is characterized by chronic inflammation and immune dysregulation. Aging of the adaptive immune system, marked by a shift from naïve to memory T-cell phenotypes, is associated with systemic \"inflammaging\", but sex-specific associations between these immunophenotypes and kidney function in older adults remain poorly understood.</p><p><strong>Methods: </strong>We analyzed cross-sectional data from 8,970 participants (aged ≥56 years) in the 2016 Health and Retirement Study (HRS) Venous Blood Study. Seventeen adaptive immune cell subsets were quantified using multiparameter flow cytometry. Kidney function was assessed using estimated glomerular filtration rate (eGFR, mL/min/1.73 m²) calculated from the 2021 race-free CKD-EPI creatinine-cystatin C equation. Survey-weighted linear regression models were adjusted for age, race/ethnicity, education, body-mass index (BMI), clinical comorbidities (diabetes, elevated blood pressure/hypertension), alcohol use, smoking status, and cytomegalovirus (CMV) serostatus. Sex-stratified analyses were conducted <i>a priori</i>, and sex interaction terms were evaluated to assess effect modification.</p><p><strong>Results: </strong>Females were older and more likely to be never smokers, CMV seropositive, and have lower eGFR, whereas males were more likely to use alcohol, smoke, have diabetes, elevated blood pressure/hypertension and higher educational attainment. In sex-stratified models, higher CD4⁺ T cells (β = 0.96, P_FDR = 0.010), CD8⁺ naïve T cells (β = 0.87, P_FDR = 0.026), Ratio of CD4⁺ to CD8⁺ T cells (β = 0.73, P_FDR = 0.036), and lymphocytes (β = 2.42, P_FDR<0.001) were associated with higher eGFR (higher kidney function) in females, while higher CD4⁺ effector memory T cells (Tem; β = -1.58, P_FDR = 0.010), CD8⁺ effector T cells (Teff; β = -1.00, P_FDR = 0.004), and CD8⁺ Tem (β = -1.40, P_FDR = 0.002) were associated with lower eGFR (lower kidney function). In males, higher IgD + memory B cells (β = 1.01, P_FDR = 0.005), IgD- memory B cells (β = 1.04, P_FDR = 0.011), and lymphocytes (β = 2.08, P_FDR<0.001) were associated with higher eGFR. Significant sex interaction was observed for CD8⁺ Tem (P_FDR = 0.015), with a nominal interaction for CD8⁺ Teff (P_FDR = 0.060). Associations were similar in sensitivity analyses and were not modified by CMV serostatus.</p><p><strong>Conclusion: </strong>Findings suggest that CD8⁺ Tem and Teff T cells may serve as sex-specific biomarkers of renal vulnerability in postmenopausal females and underscore the need for longitudinal and mechanistic studies to clarify underlying pathways.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1882462"},"PeriodicalIF":4.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repair and regeneration across the lifespan: an ontogenetic perspective.","authors":"Hugo A Barrera-Saldaña, Luis E Fernández-Garza, Fernando Guillen-Silva, Oscar R Fajardo-Ramirez, Rafael Francisco Iñigo Pavlovich, Fermín Valenzuela Gómez-Gallardo, David E Rodriguez-Fuentes, Alexia Y Avila-Villalobos, Silvia A Barrera-Barrera, Rodrigo A Somoza","doi":"10.3389/fragi.2026.1888854","DOIUrl":"10.3389/fragi.2026.1888854","url":null,"abstract":"<p><p>The capacity for tissue repair and regeneration undergoes a profound and progressive decline across the human lifespan, representing a fundamental driver of aging and chronic disease. This review establishes a comprehensive ontogenetic framework by mapping the continuous biological transition from the flawless, scarless regenerative plasticity of embryonic development to the irreversible fibrotic scarring and organ failure characteristic of senescence. We synthesize the hierarchical collapse of reparative networks across multiple biological scales. Importantly, this ontogenetic decline should not be interpreted as a purely degenerative trajectory but rather as a dynamic systems-level reprogramming in which evolutionary trade-offs prioritize tumor suppression, immune surveillance, and reproductive fitness over long-term regenerative fidelity. Recognizing this adaptive reallocation of biological resources reframes aging not simply as failure but as a predictable recalibration of repair hierarchies. At the molecular and cellular levels, the accumulation of genomic instability, unresolvable DNA damage, and mitochondrial dysfunction gradually overwhelms intracellular quality-control mechanisms. Concurrently, epigenetic drift and chronic, low-grade systemic inflammation (\"inflammaging\") dismantle the stem cell niche, driving adult stem cell exhaustion and shifting wound healing away from functional tissue replacement toward maladaptive fibrosis. Furthermore, we examine divergent, organ-specific repair trajectories. By contrasting the severe regenerative restrictions of the adult central nervous system and myocardium with the persistent, yet exhaustible, resilience of the liver, we elucidate the unique intrinsic and microenvironmental barriers that impede structural and functional recovery. Finally, we evaluate the clinical paradigm shift from passive management of age-related degeneration to active restoration of tissue integrity. By integrating systemic geroscience-which addresses the global hallmarks of aging-with targeted bioengineering and <i>in vivo</i> epigenetic modulation, contemporary regenerative medicine seeks to recreate permissive, youthful microenvironments. Ultimately, mastering these ontogenetic principles holds unprecedented potential to reactivate endogenous repair pathways, mitigate multi-organ collapse, and significantly extend human functional healthspan.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1888854"},"PeriodicalIF":4.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PolyPIMuse significantly increases fall risk: comparison of three medication evaluation tools.","authors":"András Érszegi, Réka Viola, Bettina Vargáné Szabó, Zsófia Engi, Mária Matuz, Ria Benkő, Zoltán Pető, Dezső Csupor","doi":"10.3389/fragi.2026.1903105","DOIUrl":"10.3389/fragi.2026.1903105","url":null,"abstract":"<p><strong>Introduction: </strong>Falls are a leading cause of injury and hospitalization in older adults, with pharmacotherapy identified as a modifiable risk factor. Tools for identifying potentially inappropriate medications (PIMs), such as the EU(7)PIM, PRISCUS, and FORTA lists, differ in methodology. However, their comparative performance in predicting fall risk has not been systematically evaluated. The aim of our work was to investigate the association between PIM use and fall risk among older adults and to analyze the correlations between PIM utilization based on three PIM lists (EU(7)PIM, PRISCUS, and FORTA C/D) and fall risk.</p><p><strong>Methods: </strong>In a retrospective case -control study based on real-world data from Hungarian emergency and primary care settings, we analyzed fall-related emergency department visits (n=886) in individuals aged ≥65 years and matched them with a control group from general practices (n = 1364).</p><p><strong>Results: </strong>Use of PIMs identified by all three lists was significantly associated with increased fall risk. (Use of 1 FORTA C/D active substance: AOR: 1.434; CI95%:1.120-1.838; p = 0.004; Use of 1 EU(7)PIM active substance: AOR: 1.201; CI95%: 0.907-1.591; p = 0.200; Use of 1 PRISCUS active substance: AOR: 1.390; CI95%:1.069-1.808; p = 0.014) Of the three lists, use of drugs on the PRISCUS list was most significantly associated with increased fall risk. (Use of 2 PRISCUS active substance: AOR: 1.557; CI95%:1.148-2.114; p = 0.004; Use of 3 PRISCUS active substance: AOR: 2.045; CI95%: 1.408-2.982; p = 0.000; Use of 4 PRISCUS active substance: AOR: 1.869; CI95%: 1.149-3.065; p = 0.012; Use of 5 PRISCUS active substance: AOR: 2.638; CI95%: 1.464-4.895; p = 0.002).</p><p><strong>Discussion: </strong>We introduce the concept of \"polyPIMuse\" -the use of ≥5 PIM-listed drugs -which further elevated fall risk, particularly for PRISCUS and FORTA C/D lists. Despite methodological differences, all three PIM tools proved useful in predicting fall risk. Incorporating these tools into routine medication reviews may aid fall prevention strategies in geriatric care.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1903105"},"PeriodicalIF":4.9,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual health needs and challenges among ageing women in Sub-Saharan Africa: a systematic review.","authors":"Redson Mwandama, Yankho Henry Mdoka, Oudry Mulinde, Margubur Rahaman","doi":"10.3389/fragi.2026.1803413","DOIUrl":"10.3389/fragi.2026.1803413","url":null,"abstract":"<p><strong>Background: </strong>The global ageing population is growing rapidly, with Sub-Saharan Africa undergoing a significant demographic transition. Although research on general ageing-related health outcomes in the region, such as frailty, multimorbidity, and socioeconomic deprivation, has expanded in recent years, the sexual health needs of ageing women remain comparatively understudied and inadequately addressed. This systematic review synthesizes evidence regarding the sexual health needs, challenges, and reproductive health concerns of ageing women in Sub-Saharan Africa.</p><p><strong>Methods: </strong>Scopus and PubMed databases were used to search, select, and review the publication records between 1 January 2000 and 26 May 2026. Sexual or reproductive health of women framed as ageing, older, elderly, menopausal, or postmenopausal in Sub-Saharan Africa studies were included. The PRISMA 2020 guidelines were followed for study selection and reporting. Data extraction and quality assessment were performed systematically.</p><p><strong>Results: </strong>A total of 358 records identified across Scopus and PubMed, 34 studies met the eligibility criteria and were included in the review. Six themes were identified: patterns and predictors of sexual activity in later life; menopausal symptom burden and sexual dysfunction; the intersection of HIV status and reproductive ageing; socio-cultural norms and the culture of silence; contraceptive needs and fertility ambivalence; and health-seeking behaviour and systemic barriers. Ageing women encounter multiple intersecting challenges, including age-related physiological changes, socio-cultural marginalisation, and inadequate responses from health systems.</p><p><strong>Conclusion: </strong>Sexual health needs of ageing women in Sub-Saharan Africa remain largely overlooked in research, policy, and healthcare delivery. There is an urgent need for age-sensitive sexual and reproductive health services, training for healthcare providers, and policy frameworks that acknowledge and address the unique needs of this population. Future research should prioritise empirical studies that highlight the lived experiences of ageing women and evaluate interventions aimed at enhancing their sexual health and wellbeing.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1803413"},"PeriodicalIF":4.9,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen-induced restructuring of astrocytes and vessels in organotypic mouse brain slices.","authors":"Eva Steiner, Valentin Wolfgang, Christian Humpel","doi":"10.3389/fragi.2026.1910447","DOIUrl":"10.3389/fragi.2026.1910447","url":null,"abstract":"<p><strong>Introduction: </strong>The brain exhibits high plasticity and responds to many forms of external stimuli, such as trauma, seizures, drugs, and biomaterials. Collagen is a non-toxic biocompatible protein that participates in the plastic reformation of the brain. In this study, we explored whether collagen can reconstruct astrocytes and brain vessels by using microcontact printing on organotypic mouse brain slices.</p><p><strong>Methods: </strong>Organotypic brain slices from postnatal days 8-10 were prepared and connected to collagen microcontact prints. After 2-6 weeks, glial fibrillary acidic protein-positive (GFAP⁺) astrocytes and laminin⁺ vessels were immunohistochemically stained.</p><p><strong>Results: </strong>Our data show that (1) collagen restructures laminin⁺ vessels in the whole brain slice along 50-µm-wide collagen lanes. (2) This restructuring is linked to the reformation of GFAP⁺ astrocytes in the collagen-laminin lanes. (3) In contrast to 50 µm lanes, larger 400-µm collagen spots caused a marked depletion forming large holes in the brain slice accompanied with the cell death of GFAP⁺ astroglia. (4) Preliminary/exploratory data using live cell imaging may indicate that astroglia restructure before the vessels.</p><p><strong>Discussion: </strong>Collagen has the distinctive potential to induce plasticity and the restructuring of vessels and astrocytes, however, collagen may also lead to cell death under certain conditions.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1910447"},"PeriodicalIF":4.9,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A minimal three-arm oral regimen for healthspan: mechanistic alignment with transcriptomic signals from a large parental-lifespan GWAS.","authors":"Ngo Cheung","doi":"10.3389/fragi.2026.1856979","DOIUrl":"10.3389/fragi.2026.1856979","url":null,"abstract":"<p><p>A large genome-wide association study of parental lifespan was reported in 2019. A later transcriptome-wide association study (TWAS) based on those summary statistics identified a set of transcriptional programs associated with longer genetically predicted survival, including increased brain NAD + salvage, especially NMNAT2, reduced glucose-stimulated insulin secretion, a shift toward synaptic pruning with less broad plasticity, and a glial pattern characterized by relatively greater microglial and lower astrocytic signatures, with only weak pan-tissue senescence signals. Building on those directional findings, this short communication proposes a minimal three-arm oral regimen with unequal evidentiary weight: first, the Cheung Glutamatergic Regimen, consisting of low-dose dextromethorphan potentiated by a CYP2D6 inhibitor together with piracetam and L-glutamine, as an exploratory adjunct aimed at preserving residual functional connectivity; second, daily nicotinamide mononucleotide and N-acetylcysteine with pulsed senolytics for NAD + salvage and senescence modulation; and third, GLP-1 receptor agonism for metabolic reprogramming. The NAD+/senescence arm is the primary mechanistic anchor, GLP-1 receptor agonism provides secondary metabolic support, and the glutamatergic arm is exploratory. Each arm targets a separate node within the pruning-plasticity-metabolic triad. The regimen is fully oral, uses conservative dosing, and draws on prior therapeutic or human-exposure data, although the proposed combination has no established safety profile. Although direct combination data are lacking and the foundational TWAS remains a preprint, the components show plausible but uneven mechanistic alignment with the TWAS signals and may justify carefully designed, safety-focused pilot evaluation.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1856979"},"PeriodicalIF":4.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Nutritional strategies for enhancing longevity and healthy aging.","authors":"Pintu Choudhary, Pratik S Gaikwad, Harsh B Jadhav","doi":"10.3389/fragi.2026.1898942","DOIUrl":"10.3389/fragi.2026.1898942","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1898942"},"PeriodicalIF":4.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}