Physical activity recovery after a population-level stressor varies substantially across individuals and cannot be adequately characterized by average step count alone. This study developed a source-aware personalized activity recovery representation for predicting short-term recovery slowdown using wearable step count data. Daily step counts from 226 participants across four source cohorts were analyzed, yielding 44,825 daily observations and 31,860 eligible participant-day prediction windows. Predictors were constructed only from observations available up to each prediction day and included baseline stability, early perturbation magnitude, recent recovery dynamics, local dynamic complexity, data-quality descriptors, and transferable source-domain descriptors. Recovery slowdown or reversal was defined using the baseline-normalized local slope of the subsequent 7-day window. This outcome was treated as a surrogate measure of short-term behavioral recovery momentum rather than as a clinically adjudicated recovery endpoint. The source-aware personalized activity recovery representation with XGBoost achieved an area under the receiver operating characteristic curve of 0.809, an area under the precision-recall curve of 0.702, balanced accuracy of 0.739, F1-score of 0.676, and Brier score of 0.162. Internal-external cross-validation yielded a mean area under the receiver operating characteristic curve of 0.771, indicating moderate cross-source transportability among cohorts exposed to the same first-lockdown event. SHapley Additive exPlanations identified recent recovery slope, local dynamic complexity, perturbation magnitude, baseline variability, and missingness ratio as key predictors. These findings establish a proof-of-concept for explainable wearable-derived early-warning research. Independent prospective validation, validation against functional or health-related outcomes, and local recalibration are required before clinical use or real-time intervention triggering.
Non-communicable diseases (NCDs) and their associated skeletal muscle (SkM) degeneration substantially contribute to morbidity and mortality. Interestingly, the endocannabinoid system (ECS) is increasingly recognized as an important regulator of both NCD pathophysiology and SkM plasticity. This narrative review summarizes the interplay between the ECS, NCDs and SkM degeneration - a potentially interesting triad that has not yet been comprehensively described, but may stimulate future research into the role of ECS-targeted interventions in the context of disease-associated SkM wasting.Therefore, we performed a narrative synthesis of (pre)clinical studies, focusing on alterations in ECS components (endocannabinoids, enzymes, receptors), the effects of ECS modulation (e.g. receptor (ant)agonism or enzyme inhibition), and SkM degeneration symptoms, across various (models of) NCDs. Additionally, the current literature on ECS modulation and SkM degeneration in non-disease models was summarized.The main findings show that ECS composition is consistently altered in different NCDs, including obesity, cancer (cachexia), liver disease, kidney disease, cardiovascular disease and inflammatory bowel disease. Pharmacological or genetic ECS modulation has been reported to improve several disease-related outcomes, e.g. insulin resistance, liver fibrosis and renal inflammation, predominantly in preclinical models. These NCDs also exhibit hallmarks of SkM degeneration, including atrophy, impaired regeneration, inflammation, and weakness. Notably, ECS modulation could ameliorate SkM pathology in various preclinical myopathy models, raising the hypothesis of an ECS-disease-muscle axis. However, this hypothesis requires further validation, as studies directly evaluating ECS-based interventions in disease-associated SkM degeneration remain limited. Future research should directly evaluate the existence of this potential ECS-disease-muscle axis by generating more (human) data on ECS modulation in the context of disease-associated muscle wasting.
Previous reviews have not simultaneously synthesized the effects of yoga on lower-extremity muscle strength, distinct static and dynamic balance domains, and quality of life while examining possible variation according to intervention frequency, duration, and session length in older adults. It also sought to identify standardized and effective yoga protocols and to inform appropriate intervention strategies for improving these outcomes in older adults. Following the PICOS framework, relevant studies published up to December 31, 2025, were identified through systematic searches of PubMed, Web of Science Core Collection, and Embase. After screening 3222 records identified through the database searches, 21 studies involving 1471 unique participants were included in the systematic review and meta-analysis, and the data were analyzed using RStudio. The primary unadjusted analyses suggested potential benefits for dynamic balance, lower-extremity muscle strength, and quality of life, but not static balance. After trim-and-fill adjustment, the dynamic-balance estimate became non-significant, the lower-extremity muscle-strength estimate was reduced to borderline significance, and the quality-of-life estimate remained unchanged. In conclusion, the primary unadjusted analyses suggested potential benefits of yoga for dynamic balance and lower-extremity muscle strength, but neither finding was robust to the trim-and-fill sensitivity analysis: the adjusted dynamic-balance estimate was non-significant, and the adjusted lower-extremity muscle-strength estimate was reduced to borderline significance. The quality-of-life estimate remained significant and unchanged, whereas no clear overall benefit was observed for static balance. The exploratory subgroup analyses were hypothesis-generating and did not provide sufficient evidence to recommend an optimal weekly frequency, intervention duration, or session length.
Life satisfaction is a key component of successful aging. This study investigated the correlates of life satisfaction in a sample of 127 older adults (Mage = 73.1 years, SD = 5.4) from Sardinia, an Italian island known for successful aging. Participants were assessed for global cognitive efficiency, perceived health, lifestyle habits, life satisfaction, and specific cognitive functions using the digital screening tool DIGICOG-MS. After controlling for age, education, and global cognitive efficiency, life satisfaction was significantly associated with perceived health, time spent on hobbies, verbal semantic fluency, auditory verbal learning, and immediate recall via DIGICOG-MS. A hierarchical regression analysis showed that perceived physical health, time spent on hobbies, verbal fluency, auditory verbal learning, and immediate recall were significant predictors of life satisfaction, accounting for approximately 20% of the variance (Adjusted R2 = 0.198, F(8,117) = 4.860, p < .001). Interestingly, greater usability of DIGICOG-MS was associated with lower levels of education, suggesting that the tool is highly intuitive and successfully mitigates the educational barriers often encountered in traditional paper-and-pencil neuropsychological assessments. In conclusion, these findings highlight the role of subjective health, engagement in leisure activities, executive functions, auditory verbal learning, and immediate recall in shaping life satisfaction in late adulthood, supporting the potential of DIGICOG-MS as a tool for community-based cognitive screening in older populations.
Declining aerodigestive neuromotor function is a major aspect of human aging, with impaired airway defense and swallow manoeuvres implicated in pneumonia and dysphagia. Hypoglossal motor neurons (MNs) innervate tongue muscles, essential for these behaviours. Their degeneration contributes to age-related aerodigestive dysfunctions. In neurodegenerative diseases, the ubiquitin-proteasome system (UPS) is altered, disturbing mitochondrial proteostasis. We have previously shown reduced mitochondrial abundance, dysfunction and mitochondrial fragmentation in aging hypoglossal MN somas and dendrites. However, the relationship between the UPS (pUBS65 and ubiquitinated proteins), mitochondrial fragmentation (pDRP1S616) and fusion promoting proteins (MFN2) in MN aging is unexplored. In other neurons, aging changes mitochondria within axons in an opposite way to somas and dendrites. We used Western blotting to show impairment in mitophagy-related pUBS65, increased fragmentation-promoting pDRP1S616 and unchanged MFN2. Serial Block-Face Scanning Electron Microscopy showed increased mitochondrial volume density and larger, more simplistic mitochondria in old, myelinated hypoglossal axons, while somas and dendrites showed reduced mitochondrial volume density and increased fragmentation. Our results suggest that a more nuanced compartment-specific evaluation of mitochondrial structure and function is required to fully elucidate the pathophysiology underlying age-related neuromotor dysfunction.
Objective Stair ascent, as a routine yet complex daily activity, imposes greater motor demands on older adults and is associated with an increased fall risk. Aging leads to gait adaptive changes; however, the gait adaptive changes during stair ascent across young adults, middle-aged adults, and older adults remain unclear. Methods This study employed a cross-sectional design and ultimately enrolled 36 healthy young adults, 36 middle-aged adults, and 36 older adults, with the oldest participants under 75 years of age. A three-dimensional motion analysis system combined with a surface electromyography system was used to collect gait data during stair ascent in all three groups, and differences in dynamic stability, joint coordination, and lower extremity muscle activation among the groups were further analyzed. Results Dynamic stability in the mediolateral direction during stair ascent was significantly lower in older adults than in young adults and middle-aged adults, and that trunk-pelvis transverse plane variability was significantly lower in older adults than in young adults. Regarding coordination modes, compared with young adults, middle-aged and older adults overall exhibited increased in-phase mode, decreased anti-phase mode, with lower-limb inter-joint coordination shifting toward greater proximal dominance and reduced distal dominance. Regarding muscle activation levels, older adults exhibited significantly higher activation of the medial gastrocnemius, biceps femoris, gluteus maximus, gluteus medius, and tibialis anterior than young and/or middle-aged adults. Conclusion These findings indicate that aging induces changes in coordination modes during stair ascent in middle-aged and older adults, and that the effects of aging on dynamic stability, coordination variability, and muscle function are more pronounced in older adults. This study was limited by its age range and cross-sectional design; therefore, the generalizability of the results to older adults of advanced age and their relationship with fall risk require further verification.
BACKGROUND:The role of Klotho in heart failure (HF) and its underlying metabolic mechanisms remain unclear. This study investigated how Klotho deficiency affects extracellular matrix (ECM) homeostasis and metabolic regulation in post-myocardial infarction HF (MI-HF), with a focus on aldehyde dehydrogenase 1 family member L1 (ALDH1L1). METHODS:Wild-type (WT), Klotho haploinsufficient (Klotho+/-), MI-HF, and Klotho+/--MI-HF mouse models were used. Transcriptomic and proteomic analyses were performed. RESULTS:Compared with WT, Klotho+/- mice showed 84 differentially expressed genes (DEGs) and 311 differentially expressed proteins (DEPs) enriched in ECM-related pathways. MI-HF mice exhibited similar ECM enrichment. Importantly, comparison between Klotho+/--MI-HF and MI-HF identified 201 DEPs. Proteomic KEGG enrichment analysis revealed significant enrichment of ALDH1L1-related one‑carbon metabolism and NADPH regeneration pathways, along with significant downregulation of ALDH1L1 in Klotho-deficient HF mic. CONCLUSION:Klotho deficiency is associated with exacerbated post-myocardial infarction heart failure, accompanied by significant alterations in ECM homeostasis-related molecules and ALDH1L1-mediated one‑carbon metabolism and NADPH regeneration pathways. These findings suggest that the Klotho/ALDH1L1 axis may represent a potential therapeutic target for post-myocardial infarction heart failure.
Background Over the last decades, the sphingosine kinase 1 (SK1)/sphingosine1-phosphate (S1P) axis has attracted increasing attention in cardiovascular research due to its effects under acute or chronic stress conditions. Despite this, the specific role of this molecular pathway in human heart failure (HF) remains poorly defined. Likewise, the potential of circulating S1P as a biomarker of HF has not been fully established. Methods and results To this aim, we enrolled 28 patients with HF and 16 non-HF controls. We observed that serum S1P levels were significantly reduced in HF patients compared with controls, and S1P was positively associated with left ventricular ejection fraction (EF). Further, ROC analysis demonstrated a moderate discriminatory capacity of S1P for HF. However, this relationship was partly influenced by age, as S1P levels were inversely correlated with age. Among laboratory parameters, circulating S1P levels were inversely associated with serum creatinine, suggesting a potential link between S1P signaling and cardiorenal dysfunction.Next, In differentiated human AC16 cardiomyocytes, acute β-adrenergic stimulation with isoproterenol increased SK1 and PCNA expression, whereas prolonged stimulation reduced SK1 levels, indicating a biphasic regulation of the SK1/S1P axis under sustained adrenergic stress. Similarly, hypoxic insult in AC16 cells resulted in a significant reduction in SK1 levels and increased p53 levels. Finally, in AC16 incubated withwith human blood serum from HF patients we observed a robust reduction in SK1 compared with cells incubated with control serum. Conclusions In conclusion, this study supports SK1/S1P axis as an adaptive cardioprotective mechanism activated during acute stress that becomes impaired in chronic HF-related stress. Although the association between circulating S1P and myocardial SK1 requires further investigation, reduced circulating S1P was consistently associated with HF and impaired cardiac function, supporting its potential value as a biomarker and highlighting the SK1/S1P axis as a promising therapeutic target.
BACKGROUND:Frailty represents a critical geriatric syndrome characterized by increased vulnerability to stressors, underpinned by chronic inflammation and metabolic dysregulation. This study aimed to investigate the prospective association between baseline Remnant Cholesterol Inflammatory Index (RCII) and both baseline frailty and long-term progression trajectories in two large, ethnically diverse aging cohorts. METHODS:This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS; n = 8916) and the English Longitudinal Study of Aging (ELSA; n = 5732). RCII was calculated from baseline remnant cholesterol (RC) and high-sensitivity C-reactive protein (hs-CRP). Frailty was assessed using a 32-item frailty index (FI). Linear mixed-effect models were used to examine associations between RCII tertiles and FI trajectories. RESULTS:In cross-sectional analyses, the highest RCII tertile was associated with a significantly increased baseline FI in both CHARLS and ELSA after full adjustment. In longitudinal analyses, results for RC alone indicated that while high levels were associated with consistently elevated frailty, they were not consistently associated with an accelerated rate of progression, characterized by parallel trajectories. A significant interaction between the highest RCII tertile and time was observed in CHARLS (β = 0.197, 95% CI: 0.060 to 0.335, P = 0.020) and ELSA (β = 0.055, 95% CI: 0.042 to 0.069, P < 0.001). CONCLUSION:Higher baseline RCII is consistently associated with both greater baseline frailty and is also associated with steeper frailty trajectories in older adults. These findings suggest that RCII may serve as a valuable biomarker to identify older adults at high risk for functional decline.
Intervertebral disc degeneration (IVDD) is a leading global cause of chronic pain and functional impairment. The senescence of endplate chondrocytes (EPCs) associated with the IVDD cascade, with mitochondrial homeostatic imbalance serving as the central pathological key mediator. EPCs inhabit a physiological niche defined by hypoxia, limited nutrients, and high mechanical loads, requiring precise metabolic regulation and mitochondrial quality control. This review integrates recent advances in mitochondrial biology to clarify how organelle dysfunction promotes EPC senescence. We first analyze the metabolic shift from oxidative phosphorylation to glycolysis and its impact on extracellular matrix stability. We then examine the mechanisms by which mitochondrial reactive oxygen species activate the NLRP3 inflammasome and NF-κB pathways to drive the senescence-associated secretory phenotype. Furthermore, the review discusses how fusion-fission imbalance and mitophagy failure lead to the accumulation of damaged mitochondria, and how mito-nuclear communication facilitates epigenetic remodeling to sustain senescent transcriptional programs. Finally, we evaluate therapeutic interventions targeting mitochondrial homeostasis, including targeted antioxidants, NAD+ precursors, and mitochondrial transplantation. To address the delivery challenges of avascular cartilage, the potential of cartilage-penetrating nanocarriers and gene-editing technologies is also discussed. This review establishes a theoretical framework for developing etiology-based precision therapies for IVDD.
OBJECTIVE:To examine nonlinear associations between natural environments (green and blue spaces) and biological aging in middle-aged and older Chinese adults. METHODS:We analyzed longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS). Environmental exposures were assessed using satellite-derived indicators, normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), green space coverage ratio, and blue space coverage ratio. Biological aging was quantified by frailty index (FI) and KDM-biological age acceleration (KDM-BAacc). Generalized additive mixed models (GAMMs) were employed to model nonlinear relationships; beneficial exposure ranges and optimal level were derived by differentiating the curves. Subgroup analyses examined effect modification by socioeconomic status, sex, and age. RESULTS:Significant nonlinear associations were observed between environmental indicators and biological aging. For FI, the maximum protective effect of green space occurred at 66.6% coverage, reducing FI by 0.006 (95% CI: -0.009, -0.004), the protective effect interval was (0.466, 0.784). Blue space showed maximum FI reduction of 0.014 (95% CI: -0.021, -0.008) at 10.9% coverage, with protective interval of (0.013, 0.140). When the blue space ratio was 10.9%, the protective effect on FI was the largest. For KDM-BAacc, optimal NDVI was 0.663, and optimal blue space proportion was 10.8%. Subgroup analyses revealed stronger protective effects among individuals with low socioeconomic status, women, and those aged 45-65 years. CONCLUSION:Moderate levels of green and blue spaces were associated with lower levels of biological aging. Nonlinear associations were stronger in socially vulnerable groups, suggesting that equitable nature-based planning could be a strategic public health intervention to promote healthy aging.
BACKGROUND:Aging is accompanied by chronic inflammation and altered apoptotic signaling in megakaryocytes, the precursor cells of platelets. However, it remains unclear whether activation of the JAK1-STAT1 pathway is associated with age-related megakaryocyte apoptosis and thereby promotes thrombopoiesis. OBJECTIVES:Bone marrow megakaryocytes were isolated from naturally aged C57BL/6J mice aged 4, 12, 18, 22, 24, and 26 months. Megakaryocyte proliferation, maturation, differentiation, and polyploidization were systematically characterized. Non-targeted proteomic profiling analysis was conducted to identify age-associated alterations in protein expression, while platelet counts and functional properties were simultaneously evaluated. RESULTS:Klotho expression declined significantly with age (P < 0.05), whereas pro-inflammatory cytokines and oxidative stress markers increased. Megakaryocyte proliferation decreased, while maturation and differentiation were enhanced (P < 0.05). The proportion of highly polyploid (64 N) megakaryocytes increased markedly in 24- and 26-month-old mice (P < 0.05). Apoptosis was significantly elevated, as evidenced by increased Annexin V+ cells and Caspase-3 expression (P < 0.05). Proteomic analysis revealed pronounced upregulation of IL6ST (gp130; P < 0.0001), accompanied by increased JAK1 and STAT1 expression (P < 0.05) in 24-month-old mice compared with 4-month-old controls. These changes were associated with increased platelet production, reflected by elevated reticulocyte levels and peripheral platelet counts, as well as enhanced thrombin-induced platelet aggregation and activation (P < 0.05). CONCLUSION:Age-associated inflammation is accompanied by activation of the IL6ST/JAK1-STAT1 signaling pathway, increased megakaryocyte apoptosis, and enhanced thrombopoiesis in aged mice. These findings suggest that inflammation-driven megakaryocyte remodeling may represent a compensatory mechanism for sustaining platelet production during aging and may contribute to the heightened thrombotic risk observed in older individuals.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by large-scale network disruption. While static functional connectivity (sFC) has been extensively studied, dynamic functional connectivity (dFC) and its discriminative value across the AD spectrum remain insufficiently understood. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) data from 174 participants in the Alzheimer's Disease Neuroimaging Initiative, including cognitively normal (CN, n = 44), subjective memory concern (SMC, n = 24), early mild cognitive impairment (EMCI, n = 46), late MCI (LMCI, n = 30), and AD (n = 30), were analyzed to assess group differences in sFC, dFC, and graph-theoretical metrics, as well as their associations with cognition. A BrainNetCNN model was further employed to evaluate the classification performance of sFC, dFC, and their combined features. The results revealed that sFC decreased across MCI stages but increased in AD, whereas dFC variability was predominantly reduced in the pre-dementia groups and increased in AD, particularly in frontal and temporal regions. Several static graph-theoretical metrics were significantly correlated with Mini-Mental State Examination (MMSE) scores, while dFC provided complementary information. In classification tasks, dFC showed higher accuracy than sFC in binary and five-class tasks, and their integration achieved the highest accuracy (CN vs. SMC: 89.6%; five-class: 82.7%). These findings suggest that dFC may provide complementary imaging information for characterizing stage-related network alterations and differentiating diagnostic groups across the AD spectrum.
BACKGROUND:Gait alterations are common in cognitive impairment, but how cognitive decline uniquely influences gait independent of chronological aging remains unclear. This study aimed to characterize spatiotemporal gait profiles across the dementia spectrum and to identify the mediating role of cognitive function. METHODS:This cross-sectional study included 289 community-dwelling older adults categorized into cognitively normal (CN, n = 58), subjective cognitive decline (SCD, n = 152), and cognitive impairment (CI, n = 79) groups. Eighteen gait features captured via smartphone-based computer vision were classified into spatial, temporal, and combined spatiotemporal components. Permutation entropy (PE) and autocorrelation quantified gait complexity. Generalized additive models constructed age-related gait profiles, and structural equation modeling (SEM) evaluated global cognitive mediation effects. RESULTS:Stride speed differed significantly across groups under single- and dual-task conditions. Spatial and combined spatiotemporal gait measures showed age-related reductions across all groups. Under dual-task conditions, the CI group exhibited less favorable temporal gait profiles than the CN and SCD groups. Lower cognitive status was associated with reduced spatial complexity, whereas temporal gait measures showed greater irregularity and weaker sequential dependence. SEM showed significant direct and cognition-specific indirect associations of age with the spatial (stride length) and combined spatiotemporal (stride speed) domains. For temporal components (stride time and single-support phase), age showed significant cognition-specific indirect associations but no detectable residual direct associations. CONCLUSION:Temporal gait components were associated with age primarily through cognition-related pathways and may serve as candidate digital markers of cognitive impairment, although longitudinal validation is required. Interpretation is limited by the cross-sectional design and the restricted representation of individuals with moderate-to-severe dementia.
Regular physical activity is beneficial for brain health. However, no research has explored whether physical activity level (PAL) assessed by the doubly labeled water method (PAL-DLW) is associated with brain volume and cognitive function. We investigated whether PAL-DLW, accelerometer-assessed PAL (PAL-Acc), and components of physical activity are associated with brain volume and cognitive function in older adults. We analyzed data from 49 participants with cardiometabolic or functional risks (35 female participants, age: 71.1 ± 6.9 years). PAL-DLW was calculated from total energy expenditure and estimated basal metabolic rate. PAL-Acc and components of physical activity were calculated using triaxial accelerometer data. Brain volumes were measured using T1-weighted magnetic resonance imaging. Cognitive function was assessed using the Trail Making Test and Logical Memory. Data were classified into tertiles and analyzed using an analysis of covariance and a linear trend analysis. We found no significant associations of PAL-DLW with brain volumes or cognitive function. The frontal cortex volume was associated with PAL-Acc (main effect: p = 0.006, trend: p = 0.035) and low-intensity physical activity (LPA) time (main effect: p = 0.015, trend: p = 0.009). Specifically, the dorsolateral prefrontal cortex volume was associated with PAL-Acc (main effect: p = 0.002, trend: p = 0.017) and LPA time (main effect: p = 0.005, trend: p = 0.005). Conversely, the precentral gyrus volume exhibited no associations. Our findings highlight the potential role of physical activity in mitigating volume reduction in higher-order brain regions in older adults with risk factors.
OBJECTIVE:Age-related hearing loss (ARHL) is a progressive and irreversible sensorineural impairment with incompletely understood mechanisms. This study investigates the role of protein arginine methyltransferase 6 (PRMT6) and its regulatory mechanisms in ARHL. METHODS:In vivo, D-galactose (D-gal)-induced aging mouse models were established. Auditory brainstem response (ABR), cochlear β-galactosidase activity, and PRMT6 expression were measured, and the therapeutic effects of the PRMT6 inhibitor EPZ020411 were evaluated. In vitro, D-gal-treated HEI-OC1 cells were employed. PRMT6 was silenced using siRNA. Cellular senescence and apoptosis were assessed by SA-β-gal staining and TUNEL assay. Mitochondrial function was evaluated by JC-1 staining, ROS levels, ATP content, and transmission electron microscopy. Mitophagy was determined by LC3-TOM20 co-localization and the GFP-LC3-RFP-LC3ΔG reporter system. Asymmetric arginine dimethylation of FOXG1 was measured by immunoprecipitation with the D6A8 antibody, and FOXG1 protein stability was assessed by a cycloheximide chase assay. RESULTS:Aging mice exhibited elevated ABR thresholds, increased β-gal activity, and upregulated PRMT6, all reversed by EPZ020411. PRMT6 silencing attenuated cellular senescence and apoptosis, improved mitochondrial membrane potential, elevated ATP content, reduced ROS accumulation, and ameliorated mitochondrial damage. PRMT6 silencing also enhanced autophagic flux. Notably, PRMT6 silencing did not alter FOXG1 mRNA but upregulated FOXG1 protein and decreased its asymmetric arginine dimethylation, prolonging FOXG1 half-life. FOXG1 knockdown partially reversed the enhanced mitophagy, impaired mitochondrial function, and abrogated the anti-apoptotic protection conferred by PRMT6 silencing. CONCLUSION:PRMT6 exacerbates D-gal-induced cochlear aging by promoting asymmetric arginine dimethylation of FOXG1, accelerating FOXG1 degradation, and inhibiting mitophagy. The PRMT6-FOXG1-mitophagy axis represents a potential therapeutic target for D-gal-induced cochlear aging.
BACKGROUND:Olfactory impairment is a well-established prodromal marker of neurodegeneration. However, the synergistic role of combined olfactory and gustatory dysfunction remains under-investigated in geriatric clinical practice. This scoping review aims to synthesize current evidence on the relationship between dual chemosensory decline and cognitive deterioration in aging. METHODS:Following PRISMA-ScR guidelines, we conducted a comprehensive search across PubMed, Scopus, Web of Science, and Cochrane databases for studies published between 2015 and 2025. Inclusion criteria focused on clinical research evaluating both smell and taste functions in the context of cognitive impairment and neurodegenerative diseases. RESULTS:Our analysis of the identified literature suggests that combined chemosensory deficits are significantly correlated with cognitive decline. Our findings indicate that the concurrent loss of olfactory and gustatory sensitivity could serve as potential biomarker of cortical and subcortical neurodegenerative progression, reflecting a breakdown in central multisensory integration centres critical for geriatric cognitive homeostasis. CONCLUSION:Dual assessment of olfaction and gustation may represent a promising candidate biomarker of neurodegenerative progression compared to isolated olfactory testing. We propose the integration of standardized chemosensory protocols into routine geriatric assessments as a pragmatic strategy for early cognitive risk stratification and follow-up. This approach holds significant translational potential for monitoring neurodegenerative trajectories in older adults.
Dioscin, a naturally occurring steroidal saponin isolated from various kinds of herbs with pleiotropic pharmacological properties, remains mechanistically undefined regarding its mammalian aging modulation. This study discovered that dioscin extended the lifespan of Caenorhabditis elegans. Concurrently, dioscin improved the motor function of C. elegans and reduced age pigment accumulation, while having no effect on the reproductive performance of the C. elegans. By pathway screening, we identified that dioscin extends healthspan via the endoplasmic reticulum unfolded protein response (UPRER) transcription factor XBP-1. Moreover, lifespan assays conducted on nematode mutants that the UPRER key effectors (PERK, IRE1α and ATF6) demonstrated that dioscin influences the lifespan of C. elegans through all three of these key effectors. These findings provide a foundation for further investigation into its mechanism of action in regulating mammalian aging. In this study, we used naturally aged C57BL/6 J mice in a 6-month intervention study and found that dioscin significantly reduced expression of senescence markers (p21, p16) in hepatic and skeletal muscle tissues. Furthermore, dioscin maintains proteostasis through coordinated activation of the endoplasmic reticulum unfolded protein response (UPRER) key effectors (PERK, IRE1α, ATF6, and s-XBP1). Our study provides preclinical evidence supporting dioscin as a novel intervention that ameliorates aging-associated phenotypes and highlights the pivotal role of UPRER in lifespan extension and aging suppression.
BACKGROUND:Intrinsic capacity (IC) reflects composite physical and mental capacities of aging populations. This study examined associations between IC impairments, severity, and patterns with fall-related emergency department (ED) visits in Taiwan. METHODS:We conducted a population-based cohort study using Taiwan's Integrated Care for Older People (ICOPE) database linked to National Health Insurance claims and Death Registry. A total of 244,899 adults aged ≥65 years were followed from 2022 to 2023. Six IC domains (cognition, mobility, vitality, vision, hearing, and psychological well-being) were assessed. IC levels was categorized as high (0 impairments), moderate (1-2), or low (≥3). Latent class analysis (LCA) identified IC impairment patterns. Poisson regression estimated rate ratios (RRs), adjusting for confounders. RESULTS:Over 213,528 person-years, 1485 fall-related ED visits occurred among 1375 participants (fall-related ED visit rate: 6.95 visits per 1000 person-years). Impairments in cognition (aRR = 1.23, 95% CI: 1.03-1.47), mobility (aRR = 1.58, 95% CI: 1.37-1.82), and vision (aRR = 1.20, 95% CI: 1.07-1.36) were independently associated with increased fall risk. Compared with high IC, moderate and low IC were associated with progressively higher risks of fall-related ED visits. LCA identified five IC patterns; the highest risk occurred in the physio-cognitive decline with sensory impairment (aRR = 1.87, 95% CI: 1.60-2.19), followed by all-domain impairments (aRR = 1.81, 95% CI: 1.29-2.54) and nutritional-visual-physical impairments (aRR = 1.53, 95% CI: 1.12-2.09). CONCLUSIONS:IC impairments, severity, and patterns independently predicted fall-related ED visits. Integrating ICOPE screening into primary care may enhance fall prevention strategies.
