Aging and Disease最新文献

{"title":"Aging as a Potential Modulator of Extramedullary Hematopoiesis: A Hypothesis-Generating Niche-HSPC Competence-Trigger Model.","authors":"Zoe Bezirgiannidou, Iliana Stamatiou, Konstantinos Liapis, Emmanouil Spanoudakis, Evdokia Mandala, Ioannis Kotsianidis, Timoleon-Achilleas Vyzantiadis, Efthymia Vlachaki","doi":"10.14336/AD.2026.0896","DOIUrl":"https://doi.org/10.14336/AD.2026.0896","url":null,"abstract":"<p><p>Extramedullary hematopoiesis (EMH) is a compensatory response to hematopoietic stress that occurs unevenly across disorders with ineffective erythropoiesis (IE). The mechanisms underlying differing EMH patterns despite similarly severe IE remain poorly understood. Thalassemia and congenital dyserythropoietic anemias frequently develop overt EMH, whereas myelodysplastic syndromes (MDS), despite severe IE, rarely show overt EMH. We propose the Niche- HSPC Competence-Trigger Model as a hypothesis-generating framework in which EMH expression reflects the interaction among erythropoietic trigger load, intrinsic hematopoietic stem and progenitor cell (HSPC) competence, and extramedullary niche fitness. Erythropoietic trigger load reflects the intensity and persistence of erythropoietic stress, particularly anemia and hypoxia, in disorders characterized by ineffective erythropoiesis. HSPC competence refers to the intrinsic capacity of HSPCs for proliferation and differentiation, whereas extramedullary niche fitness denotes the capacity of target tissues to support HSPC homing, engraftment, survival, expansion, and productive hematopoiesis; this capacity is shaped by stromal and vascular integrity, inflammatory and fibrotic remodeling, metabolic support, and iron availability. Within this framework, overt EMH is hypothesized to be favored when erythropoietic drive coincides with preserved HSPC competence and extramedullary niche fitness. Conversely, impaired HSPC competence or reduced niche fitness may limit overt EMH, while whether subclinical extramedullary hematopoietic activity occurs in MDS remains unresolved. We hypothesize that aging may modulate this balance by influencing both HSPC competence and niche fitness, thereby potentially contributing to the rarity of overt EMH in MDS. These hypotheses, including the contribution of aging and the possible occurrence of subclinical extramedullary hematopoietic activity, require experimental and clinical validation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF15 Induces Weight Loss with Diet- and Age-Dependent Metabolic Effects Across Tissues in Mice.","authors":"Laura Salmón-Gómez, Victoria Catalán, Beatriz Ramírez, Maite Aguas-Ayesa, Amaia Rodríguez, Sara Becerril, Gema Frühbeck, Javier Gómez-Ambrosi","doi":"10.14336/AD.2026.0702","DOIUrl":"https://doi.org/10.14336/AD.2026.0702","url":null,"abstract":"<p><p>Growth differentiation factor 15 (GDF15) is a regulator of body weight and systemic homeostasis. However, the mechanisms underlying its effects remain unclear. This study aimed to determine whether diet, age, and sex influence GDF15's metabolic effects. Male and female mice aged 8 or 64 weeks were fed a normal diet (ND) or high-fat diet (HFD) for 20 weeks and were treated subcutaneously with recombinant GDF15 or vehicle for 3 weeks. Body weight and food intake were monitored. Epididymal white adipose tissue (eWAT), subcutaneous WAT (scWAT), brown adipose tissue (BAT), liver, and gastrocnemius muscle were analyzed by histology and gene expression. GDF15 reduced body weight, with greater effects in HFD-fed and aged mice. Reduced food intake was mainly observed in young HFD-fed mice. GDF15 improved glycemic control and exerted tissue-, diet-, and age-dependent effects. The liver showed greater transcriptional changes, especially in aged mice, although GDF15 also induced tissue-specific changes in BAT, gastrocnemius muscle, and eWAT. Gdf15 expression was more strongly induced by HFD in BAT and by aging in eWAT. These findings reveal that GDF15 exerts robust metabolic effects on body weight and glucose homeostasis, with age-dependent effects on food intake. GDF15 induced tissue-specific responses influenced by diet and age that may contribute to its systemic effects. These findings suggest that additional mechanisms beyond reduced food intake may contribute to the greater weight loss observed in aged mice. Together, our findings highlight age as a key determinant of the systemic response to GDF15.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence and SASP in the Stromal Microenvironment of Breast Cancer: Dual Role in Progression and Therapeutic Options.","authors":"Maria Bogachek, David Sergeevichev, Anastasia Leonteva, Alevtina Pinova, Vladimir Richter, Anna Nushtaeva","doi":"10.14336/AD.2026.0869","DOIUrl":"https://doi.org/10.14336/AD.2026.0869","url":null,"abstract":"<p><p>Cellular senescence, a process characterized by the typically persistent cell-cycle arrest that occurs in response to DNA damage, plays a dual role in carcinogenesis. This complexity is predominantly influenced by the presence of senescent cancer-associated fibroblasts within the tumor microenvironment. While the induction of cellular senescence in early-stage tumor cells has been shown to inhibit proliferation, the action of senCAFs has been demonstrated to result in adverse consequences. It has been demonstrated that senescent cells are significant producers of the senescence-associated secretory phenotype. The SASP creates an immunosuppressive, therapy-resistant tumor microenvironment (TME) that promotes cancer progression. The current review is dedicated to the analysis of the contradictory role of senescence with focus on senCAFs in breast cancer progression. The review is devoted to the possible mechanisms of senescence induction in CAFs, their functional heterogeneity, and the key effector molecules of SASP (TGF-β, IL-6, MMPs, CXCL12, OPN) that trigger epithelial-mesenchymal transition and suppress antitumor immunity, including NK cell functionality. A particular focus has been placed on paracrine and autocrine regulatory loops, such as the OPN and CXCL12 axis, which have been shown to enhance the aggressive phenotype of both tumor cells and cancer-associated fibroblasts. The ensuing discourse will delve into the innovative strategies of the \"one-two punch approach,\" which are designed to target senCAFs with the objective of counteracting BC progression and enhancing the prognosis for breast cancer patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune State Configurations at the Amyloid-Tau Interface in Alzheimer's Disease: A Testable Framework.","authors":"Kai Zhang, Yuanyuan Zhang, Xindi Jiang, Xiu Chen","doi":"10.14336/AD.2026.0888","DOIUrl":"https://doi.org/10.14336/AD.2026.0888","url":null,"abstract":"<p><p>Neuroimmune mechanisms are central to Alzheimer's disease (AD), but a single continuum of \"more inflammation\" does not explain why similar amyloid-β (Aβ) and tau burdens are associated with different clinical trajectories, tissue responses, and treatment risks. We present a testable neuroimmune-state framework that integrates, rather than replaces, the AT(N) system, cellular-phase models, and transcriptional descriptions of disease-associated microglia and reactive astrocytes. The framework treats neuroimmune states as multidimensional, regionally heterogeneous configurations defined by pathological substrate, cellular program, biological target, vascular and aging context, and measurable patient-level readouts. We distinguish four meanings of the amyloid-tau interface: a biomarker interface, a spatial tissue interface, a cellular-state interface, and a clinical-progression interface. We then examine the hypothesis of phagocytic target switching, in which clearance pathways that support plaque compaction or debris removal may, under selected tau- and complement-rich conditions, contribute to removal of stressed but potentially functional synapses. We explicitly separate evidence from longitudinal human studies, cross-sectional biomarkers, human genetics, postmortem tissue, animal models, and in vitro systems. Current biomarkers cannot yet assign patients to validated discrete neuroimmune states; proposed state readers should therefore be probabilistic, allow regional coexistence and parallel vascular-immune trajectories, and be tested for incremental value beyond established AD biomarkers and co-pathologies. Finally, we organize immune-directed interventions by clinical evidence level and frame stage matching as a research strategy rather than a treatment algorithm. The model is useful only if its predictions can be prospectively supported or falsified.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Spermidine Supplementation on Vascular Brain Health in Older Individuals with Subjective Cognitive Decline - An Exploratory MRI Analysis.","authors":"Claudia Schwarz, Katharina Wurdack, Stefan Hetzer, Andrea Dell'Orco, Silke M Wortha, Daria Antonenko, Gloria S Benson, Nora Horn, Ulrike Grittner, Sebastian J Hofer, Tobias Eisenberg, Stephan J Sigrist, Dietmar Schmitz, Miranka Wirth, Frank Madeo, Agnes Flöel","doi":"10.14336/AD.2026.0559","DOIUrl":"https://doi.org/10.14336/AD.2026.0559","url":null,"abstract":"<p><p>Spermidine supplementation benefits brain health and function in animal models, with emerging evidence suggesting cognitive benefits in humans. However, effects on human brain health remain unclear. In this randomized, double-blind, placebo-controlled trial (SmartAge), we investigated 12-month spermidine supplementation (0.9 mg spermidine/day) in individuals with subjective cognitive decline aged 60-90 years. This exploratory secondary MRI analysis included 75 participants and assessed changes in vascular brain health measures, including cerebral blood flow (CBF), white matter microstructure, and white matter hyperintensities. Brain volume and cortical thickness were also assessed. Regression analyses were adjusted for age, sex, and baseline measures. Between-group differences were observed in regional CBF and white matter microstructure. CBF increased in the precuneus from baseline to post-intervention in the spermidine group versus placebo (between-group difference, 4.9 ml/100 g/min; 95%CI, 1.0-8.9; η²p=.11 [90%CI, .012-.250]; P=.015), with a similar trend in the posterior cingulate gyrus (3.7 ml/100 g/min; 95%CI, -.5-7.8; η²_p=.06 [90%CI, 0-.182]; P=.08). Fractional anisotropy in the cingulate gyrus white matter bundle remained stable with spermidine but decreased with placebo (.016; 95%CI, .002-.031; η²p=.06 [90%CI, .004-.208]; P=.029). CBF and fractional anisotropy changes were not substantially associated. No substantial between-group differences were found in global or regional brain volume, cortical thickness, or white matter hyperintensities, and regional MRI changes were not associated with changes in memory performance, subjective cognitive complaints, or plasma soluble intercellular adhesion molecule-1 levels. This exploratory analysis identified selected regional MRI differences in cerebral perfusion and white matter microstructure among older adults at risk for cognitive decline. These findings are preliminary and require independent confirmation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria Beyond Bioenergetics: Canonical and Non-Canonical Functions in Ischemic Stroke and Aging.","authors":"Paweł Berezka, Natalia Piekarczyk, Jan Jacek Kaczor","doi":"10.14336/AD.2026.0679","DOIUrl":"https://doi.org/10.14336/AD.2026.0679","url":null,"abstract":"<p><p>Ischemic stroke remains a leading cause of death and long-term disability worldwide, yet effective neuroprotective therapies beyond reperfusion strategies are still lacking. Emerging evidence highlights mitochondria as central regulators of neuronal fate, expanding their traditional role in cellular energy homeostasis through ATP production by oxidative phosphorylation (OXPHOS). Together with calcium buffering and redox regulation, these represent canonical mitochondrial functions. Mitochondria also regulate cellular adaptation to stress through mitochondrial quality control (MQC), mitochondrial ferritin-dependent iron buffering, signaling mediated by mitochondrial metabolites and mitochondrial DNA (mtDNA), and intercellular organelle transfer. These non-canonical functions link mitochondrial state to ferroptotic cell death, innate immune activation, and epigenetic regulation of nuclear responses. During cerebral ischemia, mitochondrial dysfunction involves impaired OXPHOS, the generation of reactive oxygen species (ROS), opening of the permeability transition pore, disruption of organelle dynamics, and dysregulation of non-canonical functions, collectively promoting neuronal injury, inflammation, and impaired recovery. These disturbances are further exacerbated by aging, which compromises MQC mechanisms, including fusion/fission balance, mitophagy, and biogenesis, and increases neuronal vulnerability. Mitochondrial signals, including mtDNA, cardiolipin, and ROS, also contribute to inflammasome activation and glial metabolic reprogramming, linking mitochondrial injury to neuroinflammation. Moreover, mitochondrial ferritin and iron buffering may influence oxidative damage and ferroptosis. Therefore, integrating canonical and non-canonical mitochondrial functions provide a broader framework for understanding ischemic injury and underscore the potential of MQC, redox regulation, iron homeostasis, and mitochondrial transfer as therapeutic targets and strategies for stroke recovery.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clearance-Repair-Activation Framework for Alzheimer's Disease: A Perspective and Validation Roadmap.","authors":"Yujia Yang, Xiufeng Zhang, Xiang Zan, Chenlong Niu, Xiangyu Wei, Pengcheng Feng, Guopeng Li, Ming Gao","doi":"10.14336/AD.2026.1040","DOIUrl":"https://doi.org/10.14336/AD.2026.1040","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a heterogeneous clinicobiological syndrome involving impaired protein clearance, neuroinflammation, synaptic and cellular injury, network dysfunction, and progressive functional decline. Amyloid-directed antibodies provide an evidence-based treatment backbone for selected patients with early symptomatic AD, but adjunctive strategies may be needed to address other disease mechanisms. This Perspective proposes a clearance-repair-activation framework for hypothesis-driven research. Clearance includes established pharmacological treatment and risk management as well as investigational drainage approaches; lymphaticovenous anastomosis (LVA) and deep cervical lymphaticovenous anastomosis (dcLVA) are considered only as research options within this broader domain. Repair includes neural stem-cell (NSC), induced pluripotent stem-cell-derived, engineered-cell, and secretome-based strategies, for which AD evidence remains predominantly preclinical. Activation encompasses invasive and non-invasive stimulation, sensory entrainment, neurofeedback, brain-computer interface (BCI) monitoring, and cognitive rehabilitation; BCI is positioned mainly as an experimental monitoring and adaptive rehabilitation platform. We define falsifiable links between clearance and repair readiness and between repair markers and activation responsiveness, consider adaptive and parallel alternatives to fixed sequencing, and integrate disease stage, heterogeneity, regulation, and combination-trial design. Informatics is limited to trial infrastructure and safety governance. The validation roadmap specifies success criteria, stop rules, interaction testing, clinically meaningful outcomes, and long-term surveillance.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker-Guided, Stage-Specific Senotherapy for Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Yunhang Chu, Wenqi Jin, Weigeng She, Qi Meng, Liwei Sun, Yan Leng","doi":"10.14336/AD.2026.1114","DOIUrl":"https://doi.org/10.14336/AD.2026.1114","url":null,"abstract":"<p><p>Cellular senescence drives inflammation and fibrosis progression in metabolic dysfunction-associated steatotic liver disease (MASLD) through the senescence-associated secretory phenotype (SASP). Existing research covers hepatocyte types, SASP signaling pathways, and senescence-targeting drugs. However, basic mechanistic understanding and precise clinical translation remain disconnected. An integrative therapeutic framework that couples senescence heterogeneity with disease stage-specific microenvironmental contexts is still lacking. This Perspective presents a hypothesis-generating translational framework and a candidate sequential trial design. The proposed sequence would combine short-term senescent cell clearance with long-term senescence modulation and metabolic maintenance. By stratifying senescence biomarkers according to clinical decision functions into patient selection markers, treatment timing markers, and response efficacy markers, and by defining candidate therapeutic windows based on disease stages, this study proposes lifestyle intervention and senescence modulation as proposed preventive strategies during simple steatosis, the testing of short-term senescent cell clearance during metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis within prospective trial settings, and careful evaluation of intervention feasibility and anticipated benefits under strict risk stratification during cirrhosis. Patients with active hepatocellular carcinoma or high-risk premalignant lesions should currently be excluded from early senolytic trials pending dedicated safety data, rather than being described as an absolute clinical contraindication. This work aims to provide an actionable and verifiable reference framework for precise translation of senescence-targeted therapy in MASLD, moving the field from whether it works toward for whom it works, when it works, and how to test it safely and effectively. All proposed thresholds, strategies, and sequences are candidate endpoints for prospective validation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Passive Blood Flow Restriction as a Countermeasure Against Disuse-Induced Muscle Atrophy: Physiological Mechanisms and Translational Evidence.","authors":"Chenghao Feng","doi":"10.14336/AD.2026.0439","DOIUrl":"https://doi.org/10.14336/AD.2026.0439","url":null,"abstract":"<p><p>Passive blood flow restriction (BFR)-intermittent vascular occlusion applied without voluntary contraction-has been proposed as a countermeasure against disuse-induced muscle atrophy in patients unable to perform conventional exercise. However, a comprehensive mechanistic synthesis integrating translational evidence with clinical applicability is lacking. This narrative review evaluated the physiological rationale, translational evidence, and safety considerations for passive BFR in load-restricted populations. PubMed/MEDLINE, Embase, and Web of Science were searched through April 2026. Studies investigating passive BFR in disuse or immobilisation contexts, together with mechanistic literature on relevant signaling pathways, were included. A three-tier evidence classification (direct, indirect, speculative) was applied throughout. Narrative synthesis followed Synthesis Without Meta-analysis (SWiM) reporting guideline due to substantial heterogeneity across study designs, populations, and protocols. Four mechanistic pathways were identified: metabolic stress and anabolic priming (indirect evidence), ischemia-reperfusion redox signaling (indirect evidence), neural modulation via metabolite-sensitive afferents (speculative evidence), and autocrine/paracrine responses (speculative evidence). The translational evidence revealed a consistent pattern: passive BFR attenuated muscle loss in postoperative (post-ACL, post-TKA) and critically ill populations characterized by elevated catabolic stress, but failed to preserve muscle mass during bed rest in healthy volunteers. To account for this divergence, a hypothesis-generating framework, the Catabolic Threshold Model is proposed, positing that passive BFR efficacy is gated by concurrent catabolic burden. A risk stratification framework including absolute and relative contraindications specific to passive BFR is presented; no serious adverse events were reported across published trials (cumulative n < 150), though safety reporting remains inconsistent. No formal risk-of-bias assessment was conducted, and the absence of reported events in such small samples should be interpreted as \"no signal detected\" rather than as evidence of safety. Passive BFR is a mechanistically plausible and apparently safe bridge intervention for the narrow therapeutic window between injury and active rehabilitation. Its clinical value appears contingent upon the presence of concurrent catabolic stress rather than mechanical unloading alone. Future mechanism-informed trials employing biomarker-guided patient stratification are needed to validate the Catabolic Threshold Model and establish standardised dosing protocols.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgolide B as a Candidate Gerotherapeutic: Evidence, Evidentiary Limits, and Translational Requirements.","authors":"Joanna Y Yang, Doris T Tu, Yun-Lin Chen, Oscar K Lee","doi":"10.14336/AD.2026.0894","DOIUrl":"https://doi.org/10.14336/AD.2026.0894","url":null,"abstract":"<p><p>Aging is a systemic process in which redox imbalance, cellular senescence, progenitor-cell dysfunction and chronic inflammation converge on frailty and functional decline, and geroscience seeks compounds that modulate several at once. What is more often missing is an explicit standard for deciding when a compound qualifies as a candidate gerotherapeutic. Ginkgolide B (GB) is a structurally defined diterpene trilactone from Ginkgo biloba and a potent antagonist of the platelet-activating factor receptor. This Review scores GB against ten stated candidacy criteria and grades the supporting evidence. In rodents, purified GB lowers pathological reactive oxygen species and senescence-associated markers, preserves osteogenic and myogenic progenitor function, and improves bone and skeletal muscle outcomes; oral administration begun at 20 months of age increased median lifespan and reduced frailty scores in female C57BL/6 mice. Two criteria are met, three partially met and five unmet: replication, generalizability across sex and genetic background, dose-response and tissue exposure, chronic human safety, and human evidence on any aging-relevant endpoint. Evidence obtained with purified GB is separated throughout from that obtained with terpene-lactone fractions or standardized extracts, since most human data cited in support of GB came from mixtures and may not transfer. Benchmarked against rapamycin, metformin, dasatinib plus quercetin, spermidine and NAD+ precursors, GB is an early-stage candidate: human exposure is intravenous, no longer than fourteen days, and confined to sepsis and acute stroke. The studies that would settle its candidacy are specified; much work remains before GB could be developed as a gerotherapeutic.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}