Frontiers in agingPub Date : 2026-09-21eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1987600
Oluwafemi Gabriel Oluwole, Paulo Adriano Schwingel
{"title":"Editorial: Biomarkers and aging: new insights for precision medicine.","authors":"Oluwafemi Gabriel Oluwole, Paulo Adriano Schwingel","doi":"10.3389/fragi.2026.1987600","DOIUrl":"https://doi.org/10.3389/fragi.2026.1987600","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1987600"},"PeriodicalIF":4.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119423","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}
Frontiers in agingPub Date : 2026-09-21eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1858090
Amanda Rao, Janice Pellow, David Briskey
{"title":"CaroRite™ for improving skin health and the visible signs of aging - a randomised, double-blind, placebo-controlled trial.","authors":"Amanda Rao, Janice Pellow, David Briskey","doi":"10.3389/fragi.2026.1858090","DOIUrl":"https://doi.org/10.3389/fragi.2026.1858090","url":null,"abstract":"<p><strong>Background: </strong>There is an increasing need to identify novel ingredients that can be safely utilized to enhance skin function and mitigate skin aging. Carotenoid supplementation shows promise in improving skin health and reducing signs of aging, owing to its antioxidant and anti-inflammatory properties.</p><p><strong>Aim: </strong>This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy of a carotenoid supplement, CaroRite™, on skin health and the visible signs of aging in healthy females.</p><p><strong>Methods: </strong>Eighty female participants aged 40-55 years were recruited and randomised to receive either CaroRite™ (containing 28-30 mg mixed carotenoids) or a placebo. Participants were instructed to take one capsule daily for 12 weeks. Outcome measures included visible signs of aging (wrinkles, skin elasticity, hydration, sebum, pigmentation, pore size, and temperature), transepidermal water loss (TEWL), dermal thickness, skin carotenoid levels, dietary carotenoid intake, and safety.</p><p><strong>Results: </strong>No significant between-group differences were observed for visible signs of aging parameters (p > 0.05). At week 12, significant between-group differences from baseline were observed for TEWL (CaroRite™ -4.58 ± 9.43 vs. placebo 0.34 ± 6.73; p = 0.011) and dermal thickness (CaroRite™ 139.50 ± 220.21 μm vs. placebo 43.90 ± 225.97 μm; p = 0.036). Skin carotenoid levels increased by 48.1% in the active group (CaroRite™ +167.09 ± 117.23 vs. placebo 9.42 ± 47.16; p < 0.001), despite no significant differences in dietary carotenoid intake between groups.</p><p><strong>Conclusion: </strong>Daily oral supplementation with CaroRite™ did not reduce the visible signs of ageing after 12 weeks, however notable improvements in skin carotenoid status, TEWL and dermal thickness was found. CaroRite™ demonstrated good bioavailability and was well tolerated. Overall, these findings support the use of CaroRite™ as part of a comprehensive approach to potentially improving skin health, particularly for enhancing skin carotenoid status and supporting underlying structural and barrier function.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, Identifier NCT06878001.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1858090"},"PeriodicalIF":4.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119333","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}
Frontiers in agingPub Date : 2026-09-18eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1866906
Kayo Moreira Bagri, Morgana Teixeira Lima Castelo-Branco, Claudia Mermelstein
{"title":"Unraveling skeletal muscle senescence in an <i>in vitro</i> cell culture model.","authors":"Kayo Moreira Bagri, Morgana Teixeira Lima Castelo-Branco, Claudia Mermelstein","doi":"10.3389/fragi.2026.1866906","DOIUrl":"https://doi.org/10.3389/fragi.2026.1866906","url":null,"abstract":"<p><strong>Introduction: </strong>Skeletal muscles are crucial for voluntary movement, posture, breathing, joint stability, and therefore are essential for maintaining overall health and quality of life. Aging, sarcopenia, cancer, immobilization, and several muscle pathologies can have an impact on muscle function, and muscle cell senescence is associated with these conditions.</p><p><strong>Methods: </strong>Here we aimed to develop a primary cell culture model to study skeletal muscle cell senescence. We induced cell cycle arrest in cultured embryonic chick muscle cells using a low concentration of cytosine arabinoside (Ara-C) for 9 days.</p><p><strong>Results: </strong>Our results show that Ara-C was able to induce several cellular senescence-associated bone fide characteristics, including reduced cell proliferation, increased β-galactosidase expression, increased reactive oxygen species production (ROS), increased p53 and p21 expression, increased muscle fibroblast cell size and nuclei numbers, increased lysosomal activity, decreased muscle differentiation (decreased muscle fiber size and decreased desmin expression), and increased secretion of IL-6, TNFα and TGFβ. Interestingly, inhibition of fibroblast growth factor receptor recovers the AraC-induced senescent phenotype in myogenic cells.</p><p><strong>Conclusion: </strong>This new experimental model could be used to deepen our understanding of the molecules and signaling pathways associated with the initiation and establishment of skeletal muscle senescence. Furthermore, this model could be used to test new drugs and therapeutic interventions aiming the amelioration of senescence-associated conditions.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1866906"},"PeriodicalIF":4.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119425","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}
Frontiers in agingPub Date : 2026-09-17eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1870256
Ainsley Ryan Yan Bin Lee, Huiqi Li, Kevin Yiqiang Chua, Woon-Puay Koh
{"title":"Association of smoking cessation with late-life frailty risk: the Singapore Chinese health study.","authors":"Ainsley Ryan Yan Bin Lee, Huiqi Li, Kevin Yiqiang Chua, Woon-Puay Koh","doi":"10.3389/fragi.2026.1870256","DOIUrl":"https://doi.org/10.3389/fragi.2026.1870256","url":null,"abstract":"<p><strong>Objective: </strong>To examine whether smoking cessation, in terms of duration and age at quitting, was associated with late-life physical frailty.</p><p><strong>Design: </strong>Prospective population-based cohort study.</p><p><strong>Setting: </strong>Chinese living in Singapore.</p><p><strong>Participants: </strong>We analyzed data from 4,574 men (mean baseline age 52.7 years, range 45-65 years) enrolled in the Singapore Chinese Health Study.</p><p><strong>Measurements: </strong>Participants self-reported smoking behaviors at four time-points over a 20-year follow-up. Physical frailty was assessed in late life (mean age 73.6 years, range 65-88 years) using a modified Cardiovascular Health Study phenotype, incorporating weakness, slowness, exhaustion and weight loss. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for association with frailty.</p><p><strong>Results: </strong>Persistent smokers had higher odds of frailty compared to never smokers (OR: 1.34; 95% CI: 1.01-1.76). Those who had quit smoking within 10 years before frailty assessment also had increased odds (OR = 1.33; 95% CI: 0.86-2.01), albeit not statistically significant. The OR (95% CI) was attenuated to 1.08 (0.76-1.51) for those quitting 10-20 years and 0.97 (0.59-1.55) for those quitting >40 years. Those who quit smoking by age 60 years had similar odds relative to never smokers: OR was 1.05 (0.74-1.48) for quitting at ages 50-60 years and further reduced to 0.86 (0.57-1.25) for quitting at ages <40 years.</p><p><strong>Conclusion: </strong>While persistent smoking was associated with increased odds of late-life physical frailty, smoking cessation for at least 10 years, or before the age of 60 years, could mitigate this risk substantially.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1870256"},"PeriodicalIF":4.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119325","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}
Frontiers in agingPub Date : 2026-09-14eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1869084
Luca Dolfi, Michael Kothmayer, Elmar Erwin Ebner, Renate Löhnert, Oliver Pusch
{"title":"Sex-specific effects of automated feeding on lifespan and reproduction in <i>Nothobranchius furzeri</i>.","authors":"Luca Dolfi, Michael Kothmayer, Elmar Erwin Ebner, Renate Löhnert, Oliver Pusch","doi":"10.3389/fragi.2026.1869084","DOIUrl":"10.3389/fragi.2026.1869084","url":null,"abstract":"<p><strong>Introduction: </strong><i>Nothobranchius furzeri</i>, commonly known as African turquoise killifish, has emerged as a powerful model organism in diverse biological research areas owing to its exceptionally short lifespan of 4-6 months. Dietary choices can significantly impact the physiology of this fish and its median longevity, prompting considerations on live versus dry food and feeding frequencies.</p><p><strong>Methods: </strong>Here, we present a novel, cost-effective, and modular automated feeding system for <i>N. furzeri</i>, capable of delivering up to 36 feedings per day with high precision. Using this system, we conducted a comprehensive, multi-parametric analysis comparing the effects of three commercially available dry diets varying in protein and fat content and live chironomid larvae (bloodworms), administered either via high-frequency automated feeding or manual twice-daily feeding.</p><p><strong>Results: </strong>A continuous diet of 24-36 feedings per day increased fish growth in weight but not in length compared to a standard twice-daily regimen. Unexpectedly, while male lifespan remained unaffected by feeding regimen or diet, females subjected to high-frequency automated feeding showed reduced longevity, particularly with high-calorie diets. Additionally, pooled reproductive profiles suggested that reproductive output was associated with dietary fat and protein content as well as feeding frequency. Greater delivered food availability, particularly under high-frequency feeding with energy-rich diets, was associated with increased egg production, reduced embryo survival, and a shortened reproductive period.</p><p><strong>Discussion: </strong>Together, these findings provide important insights for optimizing husbandry and experimental design in <i>N. furzeri,</i> supporting its broader application as a high-throughput vertebrate model.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1869084"},"PeriodicalIF":4.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076836","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":"Role of essential and trace elements in chronic myeloid leukemia: associations with serum trace element profiles and hematological parameters.","authors":"Ajay Kumar Yadav, Umesh Choudhary, Anupam Aich, Lalit Prashant Meena, Royana Singh, Shivam Tiwari, Ashish Ashish","doi":"10.3389/fragi.2026.1920709","DOIUrl":"10.3389/fragi.2026.1920709","url":null,"abstract":"<p><strong>Background: </strong>Chronic myeloid leukemia is a myeloproliferative malignancy characterized by the Philadelphia chromosome with uncontrolled expansion of myeloid cells. Trace elements are essential for cellular metabolism, DNA repair, antioxidant defence, and immune regulation, and their imbalance may influence leukemogenesis and contribute to oxidative stress, immune dysregulation, and hematological alterations. Profiling trace elements may improve understanding of CML-associated trace element alterations and identify candidate biomarkers for future validation.</p><p><strong>Material and methods: </strong>A cross-sectional study at Banaras Hindu University, India, included 93 CML patients and 93 age and sex-matched healthy controls from an eastern Indian population. Serum chromium (Cr), copper (Cu), manganese (Mn), lead (Pb), cadmium (Cd), arsenic (As), iron (Fe), selenium (Se), and zinc (Zn) concentrations were measured by atomic absorption spectroscopy. Complete blood counts were performed, and data analysed using descriptive statistics, Mann-Whitney U test, Chi-square/Fisher's exact tests, and Spearman correlation analysis.</p><p><strong>Results: </strong>CML patients exhibited significantly elevated serum concentrations of Cu, Mn, Pb, Cd, and As compared with healthy controls, whereas Cr, Fe, Se, and Zn concentrations were significantly higher in healthy controls. Several trace elements showed statistically significant associations with hematological parameters, suggesting complex interactions between elemental imbalance and CML biology.</p><p><strong>Conclusion: </strong>This study strongly shows dysregulation of essential and toxic trace elements in CML. Imbalance of selenium (Se), zinc (Zn), iron (Fe), manganese (Mn), and copper (Cu) may contribute to oxidative stress, immune dysfunction, and leukemogenesis, and toxic metals may enhance genomic instability. Trace-element profiling, especially selenium-related biomarkers, may serve as candidate biomarkers associated with CML and warrant validation in larger prospective studies.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1920709"},"PeriodicalIF":4.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076547","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}
Frontiers in agingPub Date : 2026-09-11eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1923046
Azadeh Golduzian, Erik B Erhardt, Arvind Caprihan, John C Adair, Janice E Knoefel, Jill Prestopnik, Sasha Hobson, Sephira Ryman, Andrei Vakhtin, Kiran Bhaskar, Gary A Rosenberg
{"title":"Explanatory limitations of CSF, plasma, and MRI biomarkers for inflammation and blood-brain barrier disruption in dementia.","authors":"Azadeh Golduzian, Erik B Erhardt, Arvind Caprihan, John C Adair, Janice E Knoefel, Jill Prestopnik, Sasha Hobson, Sephira Ryman, Andrei Vakhtin, Kiran Bhaskar, Gary A Rosenberg","doi":"10.3389/fragi.2026.1923046","DOIUrl":"10.3389/fragi.2026.1923046","url":null,"abstract":"<p><p>Inflammation and blood-brain barrier (BBB) disruption are increasingly implicated in cognitive decline, but it remains unclear which fluid and imaging measures best capture these processes. Participants were drawn from two overlapping research programs, MarkVCID and UNM ADRC. We studied 149 participants with Alzheimer's disease, leukoaraiosis, mixed dementia, subcortical ischemic vascular dementia, or memory impairment. BBB permeability was assessed using the albumin index (Q<sub>alb</sub>), a global blood-to-CSF leakage ratio, and dynamic contrast-enhanced MRI permeability (K<sub>trans</sub>), a regional gadolinium transfer measure. Both were treated as permeability measures that inflammation may influence rather than as direct measures of inflammation. CSF and plasma biomarkers included matrix metalloproteinases, angiogenic factors, cytokines, GFAP, NfL, pTau181, and Aβ42/40; MRI measures included PSMD, mean free water, hippocampal volume, and cortical thickness. Univariate associations were screened using Spearman correlation and AIC, and multivariable models used AIC-based stepwise selection. Diagnosis-adjusted models, bootstrap selection frequencies, penalized regression, and cross-validated R<sup>2</sup> were used as sensitivity analyses. Q<sub>alb</sub> and K<sub>trans</sub> were not significantly correlated (Spearman ρ = 0.14, p = 0.28), suggesting that they index different dimensions of BBB dysfunction without establishing biological independence. The multivariable CSF model for Q<sub>alb</sub> retained MMP-2, Flt-1, IL-8, GFAP, and NfL and explained approximately half the variance (R<sup>2</sup> = 0.53), whereas the plasma model explained less variance (R<sup>2</sup> = 0.32). For K<sub>trans</sub>, multivariable CSF, plasma, and MRI models explained R<sup>2</sup> = 0.36, 0.39, and 0.14, respectively, while PSMD was the strongest FDR-robust univariate MRI correlate. CSF-plasma correlations ranged from near zero for MMP-9 (r = -0.03) to stronger associations for NfL (r = 0.74) and IL-13 (r = 0.70), indicating that plasma cannot be assumed to substitute for CSF marker-by-marker. Q<sub>alb</sub> and K<sub>trans</sub> should be considered complementary rather than interchangeable measures. The Q<sub>alb</sub>-CSF model showed the strongest inflammation-related signal, but these findings are exploratory and require validation in independent, longitudinal cohorts before an inflammation axis can be incorporated into an ATN(V)-based framework.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1923046"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066512","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":"Rumo zhentong Yin for blood-stasis-type osteoporotic pain: protocol of a randomized, single-blind, controlled trial.","authors":"Qian Zhang, Yuanjie Song, Bailu Niu, Mianjie Liang, Jingjing Yang, Yanjie Tong, Hui Wang","doi":"10.3389/fragi.2026.1876169","DOIUrl":"10.3389/fragi.2026.1876169","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) is a metabolic skeletal disease characterized by reduced bone mass and micro-architectural deterioration, with Osteoporotic pain (OPP) as its most common clinical symptom, which markedly impairs quality of life. Modern pharmacologic treatments' limitations are obvious with population aging, so the cost-effective interventions for OPP are urgently needed. As an empirical formula, Rumo zhentong Yin has been created by the national renowned veteran Traditional Chinese Medicine (TCM) practitioner Yao Shujin for blood-stasis pain. Hence, this trial was designed to investigate the efficacy of Rumo zhentong Yin in treating blood-stasis-type OPP.</p><p><strong>Methods: </strong>A randomized, single-blind, controlled trial was designed to evaluate the efficacy of Rumo zhentong Yin combined with standard therapy for OPP. Eligible OPP patients were recruited and randomly assigned (1:1) to form either the control or treatment group. Both groups received standard treatment. The intervention lasted 3 months, with follow-up evaluations every 4 weeks. Primary outcome was pain scores; secondary outcomes included bone mineral density (BMD), bone-turnover markers, inflammatory cytokines, blood-stasis syndrome score and hematological indices.</p><p><strong>Anticipated results: </strong>To our knowledge, this trial is the first clinical study of Rumo zhentong Yin for OPP, with the primary objective to provide robust clinical evidence supporting the integration of Traditional Chinese and Western medicine for OPP.</p><p><strong>Trial registration: </strong>The trial was registered at the International Traditional Medicine Clinical Trial Registry (www.itmctr.ccebtcm.org.cn) on 2026-01-08 (ITMCTR2026000740).</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1876169"},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066463","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}
Frontiers in agingPub Date : 2026-09-10eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1887175
Abdulrahman Alangari, Jamal Arif, Fahd Al Qureshah, Fahad Alkhodairy
{"title":"Narrative review of intravenous NAD<sup>+</sup> and NAD<sup>+</sup> precursors in wellness and translational medicine.","authors":"Abdulrahman Alangari, Jamal Arif, Fahd Al Qureshah, Fahad Alkhodairy","doi":"10.3389/fragi.2026.1887175","DOIUrl":"10.3389/fragi.2026.1887175","url":null,"abstract":"<p><strong>Background: </strong>Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) is a major coenzyme critically involved in cellular metabolism, mitochondrial function, DNA repair, and stress-response signaling. Age-associated decline in NAD<sup>+</sup> levels has generated interest in NAD<sup>+</sup>-augmenting strategies; however, recent large-scale human data indicate that whole-blood NAD<sup>+</sup> concentrations do not decline with healthy aging <i>per se</i>. Despite increasing commercial use of IV NAD<sup>+</sup> therapy in wellness settings, the clinical evidence supporting its efficacy and long-term safety remains limited.</p><p><strong>Methods: </strong>Literature published between January 2018 and March 2026 was identified <i>via</i> PubMed and Google Scholar searches. Search terms were applied symmetrically across all target compounds and administration routes. Studies were included if they reported human clinical data on IV NAD<sup>+</sup> or IV NAD<sup>+</sup> precursor administration, or if they provided directly relevant mechanistic or safety evidence. Mechanistic and foundational studies published before 2018 were selectively incorporated <i>via</i> citation tracking of key included articles.</p><p><strong>Results: </strong>Available human evidence is sparse and consists primarily of small uncontrolled studies, observational investigations, and isolated case reports. Short-term IV NAD<sup>+</sup> or NMN administration has been associated with transient increases in circulating NAD<sup>+</sup> levels and changes in selected biomarkers related to oxidative stress, inflammation, and cellular metabolism. Limited exploratory reports have also described self-reported improvements in sleep-related outcomes and neurologic symptoms. However, the clinical significance of these findings remains uncertain due to small sample sizes, lack of placebo controls, heterogeneous methodologies, and short follow-up durations. Reported adverse effects include nausea, cramping, flushing, and chest discomfort, while long-term safety data are lacking.</p><p><strong>Conclusion: </strong>Current evidence regarding IV NAD<sup>+</sup> therapy remains preliminary and insufficient to support routine clinical or wellness use. Although mechanistic and translational studies provide biological rationale for NAD<sup>+</sup> augmentation, robust conclusions regarding efficacy, durability of benefit, optimal dosing, and long-term safety cannot currently be established. Larger randomized controlled trials with standardized protocols and clinically meaningful endpoints are required before IV NAD<sup>+</sup> therapy can be considered evidence-based clinical practice.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1887175"},"PeriodicalIF":4.9,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042401","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}
Frontiers in agingPub Date : 2026-09-10eCollection Date: 2026-01-01DOI: 10.3389/fragi.2026.1809697
Ahmed Alenezi, Shaun Sabico, Abdullah M Alnaami, Syed D Hussain, Mohamed S Elrobh, Nasser M Al-Daghri
{"title":"Structured lifestyle modification and biological aging: effects on PhenoAge, sclerostin, and GDF-15 in arab adults with prediabetes.","authors":"Ahmed Alenezi, Shaun Sabico, Abdullah M Alnaami, Syed D Hussain, Mohamed S Elrobh, Nasser M Al-Daghri","doi":"10.3389/fragi.2026.1809697","DOIUrl":"10.3389/fragi.2026.1809697","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle modification programs (LMP) such as diabetes prevention programs may influence phenotypic aging trajectories, but evidence in Middle Eastern populations remains limited. This study examined the effects of a structured LMP on phenotypic age (PhenoAge) as the primary endpoint and circulating sclerostin (SOST) and growth differentiation factor-15 (GDF-15) as secondary endpoints in a cohort of Arab adults with prediabetes.</p><p><strong>Participants and methods: </strong>In this randomized clinical trial (RCT), a total of 181 adults (130 males, 51 females; mean age 50.8 ± 10.9 years, body mass index, BMI 30.0 ± 4.8 kg/m<sup>2</sup>) were enrolled. Participants were allocated to either a structured LMP or Control Group (CG) and followed for 6 months. The LMP group was requested to reduce weight by 5%, moderate exercise (150 min/week), reduce fat intake (30%) and increase fiber intake (15g/1 kcal). CG was given brochure. PhenoAge was calculated and assessed alongside anthropometrics, blood biomarkers (HbA1c, fasting glucose, albumin, creatinine, GDF15, SOST), and dietary parameters at baseline and after 6 months.</p><p><strong>Results: </strong>Compared with the CG, participants in the lifestyle modification program (LMP) showed a significant reduction in PhenoAge (-4.9 vs. +1.3 years; between-group <i>p</i> < 0.001). Significant between-group improvements were also observed in weight (-5.7 kg), BMI (-2.0 kg/m<sup>2</sup>), waist circumference (-6.3 cm), and HbA1c (-0.4%; all <i>p</i> < 0.001). Neither GDF-15 nor SOST demonstrated a significant intervention-specific effect.</p><p><strong>Conclusion: </strong>A structured lifestyle intervention significantly improved PhenoAge, accompanied by improvements in metabolic parameters in Arab adults with prediabetes. Changes in GDF-15 and SOST appeared time-dependent rather than intervention-specific. These findings support lifestyle modification as a potential strategy to slow a composite clinical measure of biological aging. ClinicalTrial Registration (NCT06440681).</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"7 ","pages":"1809697"},"PeriodicalIF":4.9,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042435","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}