Introduction: This study aimed to evaluate the dose–response relationship between the Oxidative Balance Score (OBS) and a novel Gompertz law-based biological age (GOLD BioAge) and to quantify the potential mediating contributions of the Systemic Inflammation Response Index (SIRI) and uric acid to high-density lipoprotein cholesterol ratio (UHR). Methods: This cross-sectional study included 20,930 adults aged ≥20 years (weighted mean age: 47.79 years) from seven cycles of the National Health and Nutrition Examination Survey (2001–2010 and 2015–2018). Survey-weighted regressions were used to estimate independent associations of OBS with GOLD BioAge and Accelerated GOLD BioAge. Restricted cubic spline analysis was performed to assess potential nonlinearity. Robustness was assessed through sensitivity and stratified subgroup analyses. Exploratory mediation analyses using a bootstrap resampling-based framework were performed separately for SIRI and UHR to quantify their potential mediating contributions. Results: The weighted proportion of Accelerated GOLD BioAge in the overall sample was 37.57%. The OBS was inversely and linearly associated with GOLD BioAge (P for nonlinearity = 0.723). In the fully adjusted models, each 1-point increment in OBS was associated with a 0.11-year lower GOLD BioAge (β = −0.11, 95% confidence interval [CI]: −0.13 to −0.10, P < 0.001) and 5% lower odds of Accelerated GOLD BioAge (odds ratio [OR] = 0.95, 95% CI: 0.94 to 0.96, P < 0.001). Compared with the lowest OBS tertile (T1), the highest tertile (T3) had 51% lower odds of Accelerated GOLD BioAge (OR = 0.49, 95% CI: 0.43 to 0.56, P for trend < 0.001). The inverse association was directionally consistent across examined subgroups, although its magnitude differed by sex (P for interaction < 0.001). Exploratory mediation analyses showed that SIRI and UHR accounted for 21.10% and 8.30% of the OBS–GOLD BioAge association, respectively. Conclusions: In a nationally representative sample, higher OBS was linearly associated with lower GOLD BioAge, with SIRI and UHR statistically accounting for part of this association. These findings provide epidemiological evidence that a comprehensive antioxidant-oriented dietary and lifestyle profile is associated with lower biological age, warranting further prospective investigation.
Introduction. While residential greenspace has been linked to better cognitive function in older adults, it remains unclear whether short-term greenspace exposure during everyday mobility can provide immediate cognitive benefits. Stress may play a critical role in this process, as it reflects a mismatch between environmental demands and personal resources and may signal an increased need for restoration. Methods. This ambulatory assessment study examined the association between greenspace exposure and cognition in daily life, as well as the moderating role of stress. Over a two-week period, 123 older adults (aged 65–89 years) wore a GPS device that continuously recorded their mobility trajectories and carried a smartphone to complete repeated working memory tasks and experience sampling assessments of stressors approximately every two hours (seven times per day). Results. Multilevel models showed that, at the within-person level, greater-than-usual greenspace exposure in the past two hours was associated with higher-than-usual momentary working memory performance when stressor occurrence was reported, compared to moments when stressors were not reported. At the between-person level, individuals with higher overall greenspace exposure showed better working memory performance. Conclusions. These findings suggest that the cognitive benefits of greenspace exposure are context-dependent, emerging when stressors were recently present and when the need for restoration may be high. More broadly, our findings point to a dynamic, needs-based process in which everyday mobility through natural environments may support cognitive health among older adults.
Background:Osteoporosis and fragility fractures are major causes of disability, loss of independence, institutionalization, and mortality in the oldest old. Despite their exceptionally high fracture risk, adults aged ≥80 years remain underrepresented in randomized controlled trials. Diagnosis and treatment are complicated by the interaction of skeletal fragility with falls, sarcopenia, frailty, multimorbidity, cognitive and functional impairment, and competing mortality. Summary: This narrative review discusses the diagnosis, fracture-risk assessment, non-pharmacological management, and pharmacological treatment of osteoporosis in the oldest old. Bone mineral density (BMD) remains central to osteoporosis diagnosis but incompletely characterizes fracture risk at advanced age. Previous and particularly recent fractures, prevalent vertebral fractures, falls, physical performance, nutritional status, and frailty provide complementary information. Interpretation of the Fracture Risk Assessment Tool FRAX® requires particular consideration in the oldest old because competing mortality may cause 10-year fracture probabilities to plateau or decline despite increasing age-specific fracture incidence; FRAXplus® incorporates additional risk modifiers, including falls and the number and recency of previous fractures. Non-pharmacological interventions addressing nutrition, muscle function, balance, and falls complement bone-directed pharmacotherapy. Available evidence does not indicate that chronological age itself attenuates the efficacy of osteoporosis pharmacotherapy, although direct randomized fracture-endpoint evidence in adults aged ≥80 years remains limited. Risedronate and, historically, strontium ranelate provide some of the clearest fracture data specifically in this age group, whereas evidence for most other therapies derives from older-subgroup analyses, skeletal efficacy studies, observational data, or extrapolation from pivotal trials. At advanced age, renal function, cognition, mobility, adherence, caregiver support, and continuity of care increasingly influence the translation of efficacy into clinical effectiveness. Key Messages: Fracture risk in the oldest old reflects the interaction of skeletal fragility with falls, frailty, sarcopenia, and functional reserve. Available evidence supports preservation of pharmacological antifracture efficacy with advancing age, but direct evidence in octogenarians and particularly nonagenarians remains scarce. Treatment feasibility and continuity of care become increasingly relevant at advanced age. Greater representation of the oldest old in clinical trials is needed, with particular attention to fracture outcomes, treatment sequencing, time to benefit, and outcomes relevant to independence and quality of life.
Introduction Diabetic retinopathy, which occurs during extended periods of chronic hyperglycemia, is one of the main causes of vision loss. The receptor for advanced glycation end products (RAGE) plays a central role in inflammatory and angiogenic signaling, both of which contribute to the pathogenesis of diabetic retinopathy, but its therapeutic targeting in ocular disease has been insufficiently explored. Methods We evaluated topical RAGE229, a small-molecule RAGE inhibitor, and an intravitreally administered anti-RAGE antibody in a streptozotocin-induced diabetic rat model. At day 84, treatment effects were assessed using masked fundoscopic scoring, RT-qPCR, immunohistochemistry, and histological morphometry. Treated eyes were evaluated against both route-matched diabetic vehicle-control groups and paired contralateral vehicle-treated eyes. Results Both interventions reduced fundoscopic pathology and retinal Vegfa and Nfkb1 expression, whereas Ager showed only a non-significant downward trend. NF-κB p65 immunoreactivity was reduced by both treatments, while a significant reduction in VEGF-A immunoreactivity was detected only in the paired anti-RAGE antibody analysis. Morphometric analysis indicated attenuation of diabetes-associated retinal thinning with both interventions. Neither intervention altered systemic glycemic control. Although both interventions demonstrated similar overall anatomical protection, anti-RAGE antibody treatment showed more consistent effects across protein-level and structural endpoints. Conclusion These findings provide proof-of-concept evidence that local RAGE-targeted treatment may attenuate vascular, molecular, and structural manifestations of early experimental diabetic retinopathy without detectable changes in systemic glycemia. Further preclinical studies should evaluate ocular exposure, direct target engagement, functional visual outcomes, and reproducibility in larger cohorts.
Intrinsic capacity (IC) is increasingly used as an intervention outcome; however, IC composites lack a standardized scoring method, hindering comparisons across trials. To determine whether the scoring method influenced the detection of intervention effects, we applied multiple composite scoring approaches to the same data and compared their responsiveness to a 12-week exercise intervention in older adults at risk of mild cognitive impairment. Methods: Pre- and post-intervention IC data were obtained from 59 community-dwelling older adults assigned to resistance training (n=34) or stretching and flexibility (n=25). The five-domain IC composite was computed repeatedly using alternative scoring approaches: z-score (concurrent and baseline-anchored variants), percentage of maximum possible (POMP), binary classification (0/1), and a three-category ordinal scale. Responsiveness was quantified using the standardized response mean (SRM). Results: Responsiveness ranged from negligible to large for identical data, indicating that the intervention effect depended on the scoring method. The ordinal and POMP composites were the most responsive (SRM 0.74–0.88 and 0.50–0.76). Within the z-score composite, responsiveness depended entirely on the standardization anchor: the concurrent specification was insensitive (SRM ≈ 0), whereas baseline-anchoring showed moderate responsiveness (0.62–0.71). The binary scoring was the least sensitive, showing a ceiling effect. Conclusions: Ordinal three-category scoring was the most responsive, suggesting that approaches combining a fixed reference with a category-based structure are well suited for detecting change in IC. This finding requires confirmation against external criteria for IC, such as its predictive validity for adverse health outcomes, along with domain weighting and instrument selection.
