Experimental gerontology最新文献

{"title":"A randomized controlled trial of wearable accelerometer-based feedback and behavior change techniques to increase physical activity and reduce sedentary behavior in older women","authors":"Yu-Huei Wang ,&nbsp;Ting-Fu Lai ,&nbsp;Yung Liao ,&nbsp;I-Lun Cheng ,&nbsp;Ming-Chun Hsueh","doi":"10.1016/j.exger.2025.112979","DOIUrl":"10.1016/j.exger.2025.112979","url":null,"abstract":"<div><h3>Purpose</h3><div>Effective strategies are needed to address declining physical activity (PA) and prolonged sedentary behavior (SB) in older women. This study examined the impact of accelerometer-based feedback and behavior change technique (BCTs) interventions on PA and SB patterns.</div></div><div><h3>Methods</h3><div>42 healthy older women (mean age = 72.6 ± 5.2 years) were randomly assigned to an intervention group (<em>n</em> = 22) or a control group (<em>n</em> = 20). The intervention group received real-time activity feedback via a wearable device and a 12-week BCTs intervention, including PA and SB education, exercise consultation, movement notifications, and goal setting. The control group maintained their usual lifestyle and wore an accelerometer without feedback. PA (step count, light-to-vigorous intensity) and SB (total sedentary time, frequency and total duration ≥30-min sedentary bouts, and sedentary breaks) were assessed using the ActiGraph wGT3X-BT.</div></div><div><h3>Results</h3><div>After 12 weeks, the intervention group showed significant improvements in total PA (<em>p</em> = .000; ⴄ² = 0.450), daily step count (<em>p</em> = .011; ⴄ² = 0.161),≥30-min sedentary bouts frequency (<em>p</em> = .000; ⴄ² = 0.524), and total duration in &gt;30-min sedentary bouts (p = .000; ⴄ² = 0.513). No significant changes were found in specific-intensity PA, total sedentary time, and sedentary breaks.</div></div><div><h3>Conclusion</h3><div>Wearable feedback and BCT interventions effectively increased PA and reduced prolonged SB in older women.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112979"},"PeriodicalIF":4.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association and potential mediators between obstructive sleep apnea and diabetic nephropathy: A Mendelian randomization study","authors":"Yonghang He ,&nbsp;Junxiang Wang ,&nbsp;Yun Wen ,&nbsp;Bo Yi ,&nbsp;Yong Wang","doi":"10.1016/j.exger.2025.112980","DOIUrl":"10.1016/j.exger.2025.112980","url":null,"abstract":"<div><h3>Background</h3><div>Previous observational studies have reported the association between obstructive sleep apnea (OSA) and diabetic nephropathy. However, it remains to be confirmed whether this association is causal. This study aimed to investigate the causal association of OSA with diabetic nephropathy and the mediating effect of common risk factors using Mendelian randomization (MR) design.</div></div><div><h3>Method</h3><div>The study data were sourced from genome-wide association studies (GWAS). Bidirectional two-sample MR and multivariable MR analyses were conducted to assess causal relationships between OSA and diabetic nephropathy. Potential mediation by common risk factors was evaluated through two-step MR. In addition, the MR results were supported by various sensitivity and validation analyses.</div></div><div><h3>Results</h3><div>We presented genetic evidence that OSA could unidirectionally increase the risk of diabetic nephropathy (OR = 1.30; 95 % CI: 1.13, 1.50; <em>p</em> = 2.51 × 10⁻⁴). After adjusting for BMI, high blood pressure, blood glucose levels, glycated hemoglobin levels, severe insulin resistance, years of schooling, nap during day, processed meat consumption, and coffee intake, the causal effect of OSA on diabetic nephropathy remained statistically significant. Further mediation MR analysis showed that BMI and high blood pressure may mediate the causal relationship between OSA and diabetic nephropathy, with a mediation effect of 26.35 % and 9.91 %, respectively.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that genetically predicted OSA is associated with a higher risk of diabetic nephropathy. Additionally, BMI and high blood pressure are involved in the mechanism of OSA-induced diabetic nephropathy.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112980"},"PeriodicalIF":4.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sensory afferences in postural control quantified by force platform in healthy older adults: Systematic review and meta-analysis","authors":"J. Aflalo ,&nbsp;C. Truong ,&nbsp;A. Nicolaï ,&nbsp;L. Gouzer ,&nbsp;B. Morisset ,&nbsp;F. Bertin-Hugault ,&nbsp;D. Ricard ,&nbsp;F. Quijoux","doi":"10.1016/j.exger.2025.112976","DOIUrl":"10.1016/j.exger.2025.112976","url":null,"abstract":"<div><div>Postural balance in older adults is a key research focus, as impaired balance significantly increases fall risk, potentially leading to severe injury or mortality. Given age-related sensory decline, force-platform posturography assessing sensory perturbation effects could elucidate postural control deficits in aging. This systematic review and meta-analysis examines older adults' ability to maintain quiet stance during sensory perturbations.</div><div>We searched 8 databases for studies evaluating older adults' balance under various sensory conditions.</div><div>We included 64 articles in this review, for a total number of 4481 subjects. Proprioceptive and visual afferences were the most explored. Meta-analyses were conducted when several studies shared similar procedures and domain analysis for older adults (OA), older fallers (OF), and young adults (YA). They showed a significant impact of visual deprivation on older adults' balance for positional, dynamic and frequential variables, while it was significant only in the positional and dynamic domains for younger adults. When proprioception was disturbed, all the meta-analyses showed a significant impact on older adults.</div><div>We concluded that positional and dynamic variables are sensitive to sensory perturbations and therefore could be useful in geriatric balance assessment. However, we emphasize the variability in methodological approaches and reporting standards, which constrains the broader applicability of these findings. We posit that posturographic research requires standardization and the establishment of an expert consensus regarding clinically relevant variables to facilitate the integration of posturography into geriatric fall risk assessment protocols, preventive programs and rehabilitation care.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112976"},"PeriodicalIF":4.3,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Less habitual knee-bent sitting and more lying time are associated with worse frailty, mobility and balance in long-term care residents","authors":"Madeline E. Shivgulam ,&nbsp;Emily E. MacDonald ,&nbsp;Jocelyn Waghorn ,&nbsp;Chris Cartwright ,&nbsp;Andrea Mayo ,&nbsp;Derek S. Kimmerly ,&nbsp;Kenneth Rockwood ,&nbsp;Olga Theou ,&nbsp;Myles W. O'Brien","doi":"10.1016/j.exger.2025.112971","DOIUrl":"10.1016/j.exger.2025.112971","url":null,"abstract":"<div><div>The impact of habitual postures on frailty, and balance, mobility, and transfer ability, particularly among people in long-term care. We sought to characterize the time spent in detailed postures and the relationships they have with frailty and Hierarchical Assessment of Balance and Mobility (HABAM) among older adults living in long-term care. Forty-four moderate-to-severely frail long-term care residents were recruited (36 females; age: 83 ± 10 years; body mass index: 31.8 ± 7.6 kg/m²). Participants wore an activPAL on their torso, thigh, and shin for 3.6 ± 0.5 days. Frailty was determined via a 65-item index and Clinical Frailty Scale (CFS). Functional abilities were measured using the HABAM. Linear regressions, adjusted for age and body mass index, demonstrated that higher frequency of sit-to-stand transitions (18 ± 23 transitions/day), standing time (52 ± 87 min/day) and step counts (442 ± 945 steps/day) were associated with lower frailty (frailty index: 0.438 ± 0.115) and higher HABAM scores (23.2 ± 16.3/67.0; all, <em>p</em> ≤ 0.034). Knee-bent sitting (142 ± 228 min/day) was associated with higher HABAM and lower frailty index scores (both, <em>p</em> ≤ 0.002). More non-upright time (1337 ± 133 min/day) and lying time (1138 ± 372 min/day) were associated with worse frailty index and HABAM scores (all, <em>p</em> ≤ 0.021). There were no associations between straight-legged sitting (56 ± 227 min/day) with frailty index or HABAM scores (both, <em>p</em> ≥ 0.219). Overall, participant posture was mostly characterized by a horizontal thigh (sitting or lying), with ∼1 h/day upright. Intervention models promoting upright time, sit-to-stand transitions, and knee-bent sitting rather than lying are warranted for frailty and HABAM management.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112971"},"PeriodicalIF":4.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preserving intrinsic capacity in midlife women: A mixed-methods study of a personalized multicomponent intervention aligned with the WHO ICOPE framework","authors":"Ruby Yu ,&nbsp;Cecilia Tong ,&nbsp;Matthew Yu ,&nbsp;Florence Ho ,&nbsp;Angel Hui ,&nbsp;Emily Lui ,&nbsp;Jean Woo","doi":"10.1016/j.exger.2025.112973","DOIUrl":"10.1016/j.exger.2025.112973","url":null,"abstract":"<div><h3>Background</h3><div>Intrinsic capacity (IC) preservation during midlife represents a critical yet overlooked opportunity for preventing age-related functional decline. We developed <em>WomenWellness</em>, a 12-week personalized multicomponent intervention aligned with the WHO Integrated Care for Older People (ICOPE) framework, and evaluated its effectiveness and scalability potential.</div></div><div><h3>Methods</h3><div>In a multicentre randomized controlled trial conducted in Hong Kong, we enrolled 176 women with ≥1 IC domain impairment, randomizing them to <em>WomenWellness</em> (n = 117) or to a control group that received a health kit containing educational materials and lifestyle tips (n = 59). The intervention integrated personalized care, multimodal exercise, and cognitive-psychosocial activities. Outcomes included IC composite scores (range 0-6, higher = worse), domain-specific impairments, anthropometrics, physical and cognitive performance, urinary incontinence prevalence, and pain severity, analysed using generalized linear mixed models adjusted for age, education, and medication use. A parallel qualitative evaluation involved 14 focus groups (8 participant groups, 6 service provider groups) exploring intervention acceptability, feasibility, and scalability through thematic analysis.</div></div><div><h3>Results</h3><div>Participants (mean age 61.5 ± 3.6 years) receiving <em>WomenWellness</em> showed significantly greater reductions in IC composite scores than controls (β = 0.39, 95 % CI = 0.03-0.75, p = .032), with domain-specific benefits including reduced chair stand times (β = 1.57, 95 % CI = 0.51-2.63, p = .004), ASMI preservation (β = −0.32, 95 % CI = −0.60-−0.04, p = .027), cardiorespiratory fitness gains (β = −11.47, 95 % CI = −16.89-−6.04, p &lt; .001), lower malnutrition risk (OR = 0.26, 95 % CI = 0.08-0.84, p = .025), and reduced visual impairment (OR = 0.28, 95 % CI = 0.12–0.65, p = .003). Qualitative findings revealed high acceptability, with participants valuing the integrated approach and service providers emphasizing its adaptability to community settings.</div></div><div><h3>Conclusion</h3><div><em>WomenWellness</em> effectively enhanced IC in midlife women, demonstrating high acceptability, feasibility, and adaptive fidelity, thereby supporting the integration of such programs into routine midlife healthcare services.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112973"},"PeriodicalIF":4.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145590389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of Rab9-dependent mitophagy contributes to menopause-induced sarcopenia","authors":"Shota Uebo ,&nbsp;Yoshiyuki Ikeda ,&nbsp;Yoshihiro Uchikado ,&nbsp;Yuichi Sasaki ,&nbsp;Yuichi Akasaki ,&nbsp;Takuro Kubozono ,&nbsp;Mitsuru Ohishi","doi":"10.1016/j.exger.2025.112970","DOIUrl":"10.1016/j.exger.2025.112970","url":null,"abstract":"<div><div>Aim</div><div>Sarcopenia, a major cause of frailty in postmenopausal women, is linked to mitochondrial dysfunction, but the underlying mechanisms remain unclear. This study aimed to clarify whether mitophagy, a mitochondrial quality control mechanism, contributes to postmenopausal sarcopenia, to elucidate its underlying mechanism, and to assess whether it can be rescued.</div></div><div><h3>Methods</h3><div>C57BL/6 mice (12-week-old females) underwent ovariectomy to establish a menopause mouse model, or sham surgery, and the therapeutic effects of nicotinamide mononucleotide (NMN) were assessed. Human skeletal muscle myoblasts (HSMMs) differentiated under postmenopausal conditions with or without 17β-estradiol (E2), and Rab9 expression was modulated using CRISPR activation.</div></div><div><h3>Results</h3><div>Ovariectomized mice exhibited decreased muscle mass and strength. E2 deficiency in HSMMs inhibited skeletal muscle cell differentiation, promoted senescence, impaired mitochondrial function, and reduced mitophagy. However, E2 deficiency did not modulate light chain 3 and autophagy-related 7 but reduced Rab9 expression and the colocalization of Rab9 with lysosomal-associated membrane protein 2, suggesting that E2 mediates mitophagy through Rab9-dependent alternative autophagy. Furthermore, overexpression of Rab9 in E2-deficient HSMMs enhanced mitophagy, improved mitochondrial function, suppressed cellular senescence, and promoted skeletal muscle cell differentiation. The administration of NMN to ovariectomized mice increased Rab9 expression and improved sarcopenia through increased mitophagy.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that estrogen deficiency impairs mitophagy originated from Rab9-dependent alternative autophagy, leading to mitochondrial dysfunction and sarcopenia, while enhancement of Rab9 restores mitochondrial quality control and muscle function. These results identify Rab9-dependent mitophagy as a potential therapeutic target for postmenopausal sarcopenia.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112970"},"PeriodicalIF":4.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between serum uric acid and frailty: Evidence from NHANES database and perioperative geriatric frailty cohort","authors":"Jirun Wang ,&nbsp;Yaqi Han ,&nbsp;Yan Xin ,&nbsp;Yang Zhao ,&nbsp;Lei Zhang ,&nbsp;Peipei Shan ,&nbsp;Wei Feng ,&nbsp;Youzhuang Zhu","doi":"10.1016/j.exger.2025.112969","DOIUrl":"10.1016/j.exger.2025.112969","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is a common syndrome among older adults, increasing vulnerability to adverse outcomes. Serum uric acid (SUA) has been associated with several aging-related diseases, but its relationship with frailty remains inconclusive.</div></div><div><h3>Methods</h3><div>We performed an analysis using data from the NHANES (2003–2016) and a cohort study of perioperative geriatric frailty. Multivariable logistic regression and restricted cubic spline analysis were used to examine the association between SUA and frailty. Subgroup analyses and interaction were also conducted. Sensitivity analysis was conducted to evaluate the robustness of the results.</div></div><div><h3>Results</h3><div>Among 24,183 NHANES participants, 16.2 % were frail. The cohort study included 149 participants, with 57.0 % developed frailty post-surgery. Higher SUA levels were significantly associated with frailty in both populations [NHANES: adjusted OR (aOR): 1.14, 95 % CI: 1.09–1.20; <em>p</em> &lt; 0.001; Cohort: aOR: 1.49, 95 % CI: 1.04–1.91; <em>p</em> = 0.025]. Restricted cubic spline regression revealed a U-shaped relationship between SUA and frailty, with OR lowest at 4.3 mg/dL. The association between SUA and frailty was significantly stronger in females than in males (adjusted OR: 1.24; 95 % CI: 1.16–1.32). Sensitivity analysis confirmed the robustness of the association between SUA and frailty (aOR: 1.17; 95 % CI: 1.11–1.23).</div></div><div><h3>Conclusions</h3><div>SUA is significantly associated with frailty in both community and surgical populations. In community population, a U-shaped relationship was observed, whereas only high SUA levels predict frailty perioperatively. Females are more susceptible to SUA-related frailty.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"212 ","pages":"Article 112969"},"PeriodicalIF":4.3,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145544407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroepiandrosterone opposes cardiac aging via NFκB/IL-10/Sirt1/Nrf2 mediated pathway in aged rats","authors":"Yahya M. Naguib ,&nbsp;Mohamed S. Rizk ,&nbsp;Reda A. A. Abo-Elsoud","doi":"10.1016/j.exger.2025.112968","DOIUrl":"10.1016/j.exger.2025.112968","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular aging is characterized by structural and functional deterioration of the heart, mediated by chronic inflammation, oxidative stress, and impaired cellular defense pathways. Dehydroepiandrosterone (DHEA), a steroid hormone with known anti-inflammatory and antioxidant properties, declines with age and may have therapeutic potential in ameliorating cardiac aging. The aim of the present study was to test the hypothesis that replenishing DHEA can counter the age dependent decline in cardiac functions. The possible underlying mechanisms were also tested.</div></div><div><h3>Methods</h3><div>Thirty male Wistar rats were divided into three groups: control, aged, and aged treated with DHEA (30 mg/kg/day via intraperitoneal injection for 4 weeks). Cardiovascular parameters (SBP, DBP, HR), biomarkers of myocardial insult (troponin I, CK-MB, myoglobin, LDH, and GP-BB), cardiac performance (lactic acid and treadmill endurance test), markers for inflammation (NFκB and IL-10) and oxidative stress (MDA and TAC), and the gene expression of NFκB, IL-10, Sirt1 and Nrf2 were assessed.</div></div><div><h3>Results</h3><div>Aging was associated with significant increases in SBP, DBP, HR, serum levels of myocardial injury markers, lactic acid, NFκB and MDA, and cardiac muscle NFκB gene expression. Aging was also associated with reduced cardiovascular endurance, serum levels of IL-10 and TAC, as well as cardiac muscle IL-10 Sirt1 and Nrf2 gene expression. Administration of DHEA significantly improved all affected parameters compared to untreated aged rats. Nevertheless, control-comparable values were not achieved. Notably, DHEA downregulated cardiac muscle NFκB while it upregulated IL-10, Sirt1, and Nrf2 gene expression, suggesting a possible common anti-inflammatory/antioxidant pathway.</div></div><div><h3>Conclusion</h3><div>DHEA supplementation in aged rats mitigated cardiovascular aging by improving hemodynamic parameters, reducing myocardial injury, demoting inflammation, enhancing antioxidant capacity, and activating key protective genes. Our findings support a potential therapeutic value of DHEA in modulating age-dependent decline in cardiac functions through a possible NFκB/IL-10/Sirt1/Nrf2 pathway.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"212 ","pages":"Article 112968"},"PeriodicalIF":4.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration and glial activation related blood biomarkers in Alzheimer's disease: A systematic review and an updated meta- analysis","authors":"Rasoul Ebrahimi ,&nbsp;Amir Abbas Salehi Amniyeh Khozani ,&nbsp;Mohammad Mahdi Masouri ,&nbsp;Mojtaba Seifi ,&nbsp;Anahita Hashempoor ,&nbsp;Sana Mohammad Soltani ,&nbsp;Shokoofe Noori","doi":"10.1016/j.exger.2025.112960","DOIUrl":"10.1016/j.exger.2025.112960","url":null,"abstract":"<div><h3>Background and objectives</h3><div>This systematic review and meta-analysis aims to evaluate blood biomarkers associated with neurodegeneration and glial activation, specifically GFAP, NfL, YKL-40, MCP-1, neurogranin, GAP-43, S100B, and NSE, in individuals diagnosed with Alzheimer's Disease (AD).</div></div><div><h3>Methods</h3><div>PubMed and Web of Science were searched until February 20, 2025, without restrictions on language, time, or study design, to identify studies reporting blood levels of the biomarkers in individuals along the AD continuum (including those with MCI and AD dementia) and cognitively unimpaired (CU) controls. Pooled effect sizes were calculated using the Hedges' g method with a random-effects model.</div></div><div><h3>Results</h3><div>A total of 3684 studies were identified, with 144 meeting inclusion criteria (AD continuum <em>n</em> = 42,587, CU <em>n</em> = 30,000). Compared with CU individuals, patients on the AD continuum showed higher levels of NfL (SMD = 0.82, 95 % CI 0.67–0.96, <em>p</em> &lt; 0.05), GFAP (SMD = 1.57, 95 % CI 1.26–1.88, p &lt; 0.05), and YKL-40 (SMD = 1.39, 95 % CI 0.56–2.21, p &lt; 0.05). Both biomarkers were significantly elevated in more advanced stages of the disease, particularly in AD dementia compared with mild cognitive impairment (MCI) (GFAP SMD = 0.79, 95 % CI 0.55–1.03, <em>p</em> &lt; 0.05; YKL-40 SMD = 0.98, 95 % CI 0.17–1.79, <em>p</em> = 0.02). No significant differences were found for MCP-1, neurogranin, S100B, or NSE.</div></div><div><h3>Discussion</h3><div>Our findings suggest that these biomarkers reflect AD-related pathology. Limitations include the lack of cultural and linguistic diversity in the study populations. Future research should focus on biomarker-defined AD populations for further validation</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"212 ","pages":"Article 112960"},"PeriodicalIF":4.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of ninjin'yoeito on age-related decline in responsiveness of the brain reward system in mice","authors":"Shinji Miyazaki,&nbsp;Keita Mizuno,&nbsp;Yoshiki Ikeda","doi":"10.1016/j.exger.2025.112967","DOIUrl":"10.1016/j.exger.2025.112967","url":null,"abstract":"<div><div>The reward system involved in the regulation of appetite and motivated behaviors involves mesolimbic dopamine signaling from the ventral tegmental area (VTA) to the nucleus accumbens (Nac). Age-related loss of dopaminergic neurons and weakening of dopamine signals reportedly cause reward system dysfunction, and similarly, age-related changes in microglia in the VTA have been suggested to be involved in this dysfunction. Ninjin'yoeito (NYT), a traditional Japanese herbal medicine, has been reported to improve anorexia, apathy, and the decline in motivation-related behavior in frail Alzheimer's disease patients and older animal models. Although behavioral and electrophysiological analyses suggest that NYT may affect dopamine signaling, the effects of NYT on the reward system remain unclear. The present study aimed to determine whether NYT modulates dopamine-mediated reward circuits in older mice, and whether its effects are linked to microglial modulation in the VTA. Repeated NYT administration restored the responsiveness of dopaminergic neurons in the VTA and increased dopamine release in the Nac, causing an increase in grooming behavior with sucrose stimulation in older mice. Although NYT did not affect cellular senescence of dopaminergic neurons or glial cells, including astrocytes and microglia, it reduced phosphorylation of TANK-binding kinase 1 and expressions of NLRP3 and IL-1β in the VTA. Furthermore, NLRP3 expression in VTA microglia, but not astrocyte, was attenuated by NYT. Our results suggest that NYT may suppress age-related inflammation in the VTA, thereby ameliorating age-related hypovolition.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"212 ","pages":"Article 112967"},"PeriodicalIF":4.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}