ObjectiveTo investigate the impact of mild-to-moderate frailty on the long-term prognosis of hospitalized elderly patients with type 2 diabetes mellitus(T2DM).MethodsA retrospective cohort study was designed, which contains T2DM patients aged ≥65 years and hospitalized in the Department of Geriatrics at Peking Union Medical College Hospital(PUMCH) from 2014 to 2022. Frailty status of those T2DM patients was assessed using the Clinical Frailty Scale(CFS), and the data of comorbidities, functional status, nutritional indices, and geriatric syndromes were collected. The primary endpoint was all-cause mortality, with secondary endpoints including rehospitalization rate and severe disability. Cox proportional hazards regression models were employed to analyze the association between mild-to-moderate frailty and outcomes.ResultsA total of 367 elderly T2DM patients were enrolled, comprising 164 males(44.7%) and 203 females(55.3%), with an age ranging from 65 to 93 years(median age 74 years). According to the CFS assessment, 115 patients(31.3%) were identified as mild-to-moderate frailty(including 56 with mild frailty and 59 with moderate frailty). During a follow-up period of 2.3-10.3 years(median 5.6 years), the frail group exhibited significantly higher rates of severe disability, unscheduled rehospitalization, and all-cause mortality compared to the non-frail group. Multivariable Cox regression analysis revealed that mild-to-moderate frailty was an independent risk factor for severe disability(HR=4.82, 95% CI: 1.57-14.79, P=0.006).ConclusionsThe presence of mild-to-moderate frailty significantly increases the risk of long-term adverse outcomes. Clinical practice is recommended to strengthen frailty screening and comprehensive intervention for elderly T2DM patients to improve their quality of life and clinical outcomes.

ABSTRACT The Asian Sarcopenia Working Group has released its latest 2025 consensus update. This narrative review interprets key changes in the AWGS 2025 consensus including: for the first time the working group establishes a conceptual framework centered on muscle health promotion, proposes diagnostic thresholds for sarcopenia in middle‐aged people, simplifies the diagnostic criteria for sarcopenia to only require the concurrence of low muscle mass and low muscle strength, and regards physical performance as an outcome indicator. The consensus aims to identify and intervene in muscle decline at an early stage, providing directional guidance for muscle health management across the life course.

Held on August 17, 2025 in Guangzhou, the inaugural International Exchange Forum of the Chinese Geriatrics Society marked a significant milestone in advancing geroscience and fostering global collaboration in China. The forum brought together leading international experts and emerging Chinese researchers to present the latest advances in aging research. Presentations covered various topics, such as musculoskeletal aging (mitochondrial dysfunction, muscle-bone communication, and exosome-mediated mechanisms in sarcopenia and osteoporosis), cardiovascular aging (tyrosine kinase inhibitor- and anthracycline-induced cardiotoxicity), metabolic regulation (sarcopenic obesity and the gut-muscle axis), neurodegenerative interfaces (androgen-mediated monocyte-microglia interactions in Alzheimer's disease), and geriatric assessment (muscle-specific strength, intrinsic capacity, and gait biomarkers). There was a particular focus on novel mechanistic insights, such as RNA epitranscriptomics, mitochondrial homeostasis, and inter-organ communication, as well as on strategies for early risk prediction, intervention, and personalized management. The forum also emphasized the importance of addressing sex-specific differences and translating basic discoveries into clinical applications. As a platform designed to promote academic dialogue and collaboration, the forum successfully brought together the Chinese and global geroscience communities. It emphasized the necessity of multidisciplinary and international efforts to address the challenges posed by population aging. Moving forward, sustained partnerships, data sharing, and capacity-building initiatives will be essential to accelerating the development of evidence-based, scalable solutions for healthy aging in China and beyond. This event sets a precedent for future exchanges that integrate scientific innovation with clinical practice to improve the health and quality of life of aging populations worldwide.

​Background: Sarcopenia is associated with a twofold higher risk of falls, frailty, and mortality. The 2025 Asian Working Group for Sarcopenia (AWGS) introduces agestratified diagnostic cutoffs, which enables earlier identification of muscle decline. Although several risk factors for sarcopenia have been identified, previous studies have focused on individual associations without quantified their relative contribution to disease burden. We therefore aimed to examine potentially modifiable risk factors and to quantify their population-level contribution using population attributable fractions (PAFs). Methods: We conducted a multicenter, cross-sectional study of 20484 adults aged 60 years or older from the Chinese Registry for Comprehensive Geriatric Assessment. Sarcopenia was defined according to the 2025 AWGS criteria. Associations were assessed using Poisson regression with robust variance estimators to obtain prevalence ratios (PRs). PAFs were calculated using PRs and exposure prevalence. Communality-based weighting was applied to account for correlation among risk factors. Sensitivity analyses assessed robustness. Findings: After accounting for shared variance, 22·2% (95% CI 19·7-25·1) of cases were attributable to 13 modifiable risk factors. For health-related conditions, cognitive impairment was the largest contributor (adjusted PAF 4·8%, 95% CI 4·1–5·5), followed by cerebrovascular disease (1·85%, 95% CI 1·45–2·28). For lifestyle behaviors, smoking and drinking contributed 2·22% (95% CI 1·68–2·77) and 1·62% (95% CI 1·04–2·21), respectively. Residential and care environment factors also showed varying contributions. Interpretation: Approximately one-fifth of sarcopenia was attributable to modifiable risk factors. A comprehensive public health system to control and manage sarcopenia is encouraged. Cognitive function training, restricting smoking and drinking might be an important part of sarcopenia management.

Background: Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass and strength, representing a major contributor to disability and increased mortality in older adults. Current diagnostic frameworks increasingly emphasize muscle quality alongside quantity, creating a clinical need for bedside tools that can objectively assess muscle mechanical properties. Shear-wave elastography (SWE), an ultrasound-based technique that quantifies muscle stiffness, has emerged as a promising biomechanical biomarker of muscle quality. Aim: This narrative review evaluates the evidence supporting SWE for assessing muscle quality and its association with aging, sarcopenia, and functional outcomes. Methods: We searched PubMed, Embase, and Web of Science (from January 2010 to December 2025) using terms related to elastography and sarcopenia. Based on relevance and methodological quality, approximately 50 key studies were selected for in-depth discussion and synthesis. Synthesis: Observational studies consistently demonstrate that SWE detects age-related reductions in muscle stiffness, which correlate significantly with declines in muscle strength and physical performance. Unlike conventional B-mode ultrasound, which primarily provides morphological parameters, SWE directly reflects intrinsic tissue mechanics, enabling more direct assessment of muscle quality. In high-risk populations such as patients with type 2 diabetes, reduced muscle stiffness is also associated with sarcopenia and poor functional outcomes. However, reported stiffness trends with aging remain heterogeneous, and validated diagnostic thresholds are lacking. Stiffness changes vary by muscle group, acquisition protocol, and loading state. Clinical implementation is currently limited by inter-device variability, operator dependence, and sensitivity to muscle loading conditions. Conclusions: Current evidence suggests that SWE holds promise as an adjunctive research tool for assessing muscle quality and risk stratification, but it is not yet ready for standalone clinical diagnosis due to methodological heterogeneity, lack of validated cutoffs, and limited longitudinal data. Future large-scale, longitudinal, multicenter studies with standardized protocols are needed to establish its definitive diagnostic utility.

ABSTRACT Sarcopenia, defined as progressive loss of skeletal muscle mass and function, occurs during aging and has also been recognized for its detrimental effects in various disease states. Its prevention and management represent a critical aspect of geriatric care and multi‐morbidity management. As a systemic disorder, extracellular vesicle‐transported miRNAs mediate both intrinsic muscle pathology and multifaceted organ crosstalk. This review comprehensively summarizes and discusses the roles of EVs‐miRNAs in sarcopenia under physiological aging and pathological conditions, and their emerging potential as diagnostic biomarkers and engineered therapeutic targets.

Adipose-derived stem cells (ADSCs) demonstrated therapeutic potential in various fibrotic diseases, with their paracrine proteins playing a crucial role. Nonetheless, the principal paracrine factors of ADSCs responsible for antifibrosis have not yet been well identified. To address this issue, we initially confirmed that ADSCs could attenuate fibrosis and suppress TGF-β1 in bleomycin-induced skin fibrosis mouse models. RNA-sequencing of the cocultured fibroblasts demonstrated that ADSCs effectively inhibited the TGF-β/Smad2 signaling pathway in fibroblasts through the paracrine approach. Proteomic analysis of the cell supernatant (CS) demonstrated a significant upregulation of 97 proteins in the secretome of ADSCs, among which decorin (DCN) exhibited a particularly elevated level of overexpression. Protein-protein interaction (PPI) network analysis indicated a strong correlation between DCN and TGF-β1, with DCN effectively trapping TGF-β1 through core protein binding. Cell experiments demonstrated that DCN could effectively inhibit TGF-β1-induced fibroblast proliferation. Therefore, it was concluded that DCN was a crucial protein in ADSC secretome that exerted antifibrotic effects by inhibiting TGF-β1. This study conducted an in-depth insight into the paracrine function of ADSCs through transcriptome and proteome analysis, identifying DCN as an essential paracrine factor mediating the antifibrotic effect of ADSCs, which could provide valuable theoretical support for the use of ADSC secretions as well as DCN in the treatment of fibrotic diseases.

A poor prognosis within 1 year of discharge is important when making decisions affecting postoperative geriatric inpatients. Comprehensive geriatric assessment (CGA) plays an important role in guiding holistic assessment-based interventions. However, current prognostic models derived from CGA and clinical data are limited and have unsatisfactory performance. We aimed to develop an accurate 1-year mortality prediction model for patients discharged from the geriatric ward using CGA and clinical data. This longitudinal cohort study analysed data from 816 consecutively assessed geriatric patients between January 1, 2018 and December 31, 2019. Models were constructed using Cox proportional hazards regression and their validity was assessed by analysing discrimination, calibration, and decision curves. The robustness of the model was determined using sensitivity analysis. A nomogram was developed to predict the 1-year probability of mortality, and the model was validated using C-statistics, Brier scores, and calibration curves. During 644 patient-years of follow-up, 57 (11·7

Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

BACKGROUND:Chronic intestinal pseudo-obstruction (CIPO) is a rare and debilitating disorder, characterized by severe impairments in gastrointestinal motility. The affected sites include the enteric/intrinsic autonomic nerves (neuropathy), intestinal smooth muscle cells (myopathy), and interstitial cells of Cajal (mesenchymopathy). The etiology can be genetic, idiopathic, or acquired. Owing to its nonspecific clinical presentation and lack of definitive diagnostic methods, misdiagnosis of CIPO is common. CASE SUMMARY:This case involved an older male with insidious onset in adolescence who presented with postprandial bloating, intermittent diarrhea, and weight loss. During the disease course, the patient experienced two episodes of intestinal obstruction. Imaging revealed multisegmental digestive tract abnormalities (gastric emptying disorder, significant duodenal dilatation, and segmental jejunal dilatation). Whole-exome sequencing revealed a rare MYH11 mutation [NM_001040113.2: C.5819del (p.Pro1940HisfsTer91)], confirming hereditary myopathic CIPO. CONCLUSION:This report adds to our current understanding of CIPO etiology by reinforcing the role of MYH11 variants in the pathogenesis of the CIPO phenotype.

Despite its rapid economic rise over the past four decades, China now grapples with the challenge of accommodating and supporting its expanding aging population. In 2020, 18

Insulin resistance, a hallmark of type 2 diabetes, accelerates muscle breakdown and impairs energy metabolism. However, the role of Ubiquitin Specific Peptidase 2 (USP2), a key regulator of insulin resistance, in sarcopenia remains unclear. Peroxisome proliferator activated receptor γ (PPARγ) plays a critical role in regulating muscle atrophy. This study investigates the role of deubiquitinase USP2 in mitigating muscle atrophy. Our findings revealed reduced USP2 expression in skeletal muscles of patients with type 2 diabetes. In mouse models of diabetes- and dexamethasone (DEX)-induced muscle atrophy, USP2 expression was downregulated in skeletal muscles. Usp2 knockout exacerbated muscle loss and functional impairment induced by diabetes or DEX. Moreover, skeletal muscle-specific Usp2 knockout further aggravated muscle loss and functional impairment induced by diabetes. Local injection of AAV-Usp2 into the gastrocnemius muscles of diabetic mice increased muscle mass, and improved skeletal muscle performance and endurance. It enhanced insulin sensitivity in diabetic mice, shown by lower fasting serum glucose and insulin levels and better glucose tolerance. Mechanistic analysis showed USP2 directly interacted with PPARγ by deubiquitinating it, stabilizing its protein levels, enhancing insulin signaling and sensitivity, and maintaining muscle mass. Loss of PPARγ abolishes the regulatory effects of USP2 on insulin sensitivity and muscle atrophy. MYOD1 activates USP2 transcription by binding to its promoter region. This study demonstrates the protective role of USP2 in mitigating muscle atrophy by stabilizing PPARγ through deubiquitination, particularly in models of diabetic and DEX-induced muscle atrophy. Targeting the USP2-PPARγ axis may offer promising therapeutic strategies for metabolic disorders and sarcopenia.

The overexpression of heat shock protein 90 (Hsp90) in mitochondria is a key mechanism for tumor cells to evade apoptosis, and is closely related to tumor invasion and the development of drug resistance. Shepherdin is an artificial small molecule peptide consisting of nine amino acids, which can selectively bind to the ATP pocket of Hsp90, thereby triggering mitochondria-dependent apoptosis, thus rendering it a potential anticancer drug. However, shepherdin itself is difficult to be taken up by cells, let alone enter the cell mitochondria. To overcome this challenge, we used triphenylphosphonium (TPP) to modify branched polyethylenimine (bPEI), resulting in a positively charged carrier with mitochondrial targeting capabilities. Additionally, poly (gamma-glutamic acid) (PGA) was employed to conjugate shepherdin to form the negatively charged PGA-shepherdin. As a result, stable TPPbPEI/PGA-shepherdin polyplexes were obtained through electrostatic interaction complexation. Cell colocalization experiments exhibited that the polyplexes could deliver shepherdin into the mitochondria, resulting in shepherdin accumulation in mitochondria, which subsequently inducing mitochondrial membrane depolarization and, ultimately, significantly increasing tumor cell apoptosis. Consequently, the TPP-bPEI/PGAshepherdin polyplexes demonstrated remarkable anti-tumor effect on both MDA-MB-231 cells and tumorbearing mice, indicating that the mitochondria targeted shepherdin delivery system held great potential for clinical tumor therapy.

Scleroderma is a chronic autoimmune connective tissue disease characterized by progressive skin fibrosis, vascular dysfunction, and immune dysregulation. Current therapies remain largely ineffective in reversing established fibrosis and are limited by systemic side effects. In this study, we developed a novel therapeutic strategy combining microneedle (MN)-mediated transdermal delivery with NRF2-overexpressing exosomes (NRF2-OE Exos) to locally enhance antioxidant, anti-fibrotic, anti-inflammatory, and pro-angiogenic effects in scleroderma. Exosomes were isolated from NRF2-OE adipose-derived stem cells (ADSCs) and incorporated into GelMA/PEGDA-based dissolvable MNs. These MNs demonstrated excellent mechanical strength, minimal invasiveness, sustained exosome release, and efficient cellular uptake in vitro. Functional assays showed that NRF2-OE Exos-loaded MNs significantly enhanced endothelial tube formation, preserved fibroblast mitochondrial integrity, and promoted macrophage polarization toward a reparative phenotype. In a bleomycin-induced murine scleroderma model, MN treatment reduced dermal thickening, collagen deposition, and α-SMA expression while promoting vascular regeneration and immunomodulation. Mechanistically, transcriptomic analysis revealed that NRF2-OE Exos suppressed pro-fibrotic Wnt and Hippo signaling pathways and activated calcium and cAMP signaling pathways. Moreover, NRF2-OE Exos alleviated mitochondrial dysfunction and ferroptotic injury by upregulating antioxidant and lipid peroxidation defense genes. Collectively, this study demonstrates that MN-mediated delivery of engineered exosomes offers a promising, localized, and multifaceted therapeutic approach for scleroderma, with strong translational potential.

Chronic wounds present a significant clinical challenge for which advanced dressings with regenerative properties are essential for effective healing. This study developed an exosome (Exo)-loaded microneedle (MN) patch. The patch was fabricated based on a metal-organic framework (MOF) through a self-assembly electrostatic adsorption process, with the objective of enhancing wound healing. The large surface area, high porosity, and positive charge of the MOF enable the efficient loading of negatively charged exosomes via electrostatic interactions. As the MNs degrade, the MOFs release both zinc ions, with antibacterial, anti-inflammatory, and angiogenic properties, and exosomes, which are internalized by cells and enhance cellular regeneration. In vitro and in vivo studies confirmed the effectiveness of the MN-MOF-Exo patch in diabetic wound healing, while RNA sequencing analysis revealed that the patch accelerated wound healing by upregulating key genes, activating the ERK1/2 and PI3K-Akt signaling pathways, and facilitating angiogenesis, cell migration, and extracellular matrix remodeling. This innovative approach combines the efficient electrostatic self-adsorption of exosomes onto the MOF within a MN structure, enabling the precise, minimally invasive, and effective delivery of therapeutic agents directly to the wound site. Furthermore, the regenerative mechanisms of the MN-MOF-Exo patch were investigated, revealing how tissue repair is promoted and how healing is accelerated through enhanced cellular regeneration and localized therapeutic effects.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Oral diseases have emerged as one of the most prevalent non-communicable diseases (NCDs) worldwide, with a high global average prevalence of 45

Late-onset rheumatoid arthritis (LORA) refers to rheumatoid arthritis (RA) with initial symptoms and signs appearing after the age of 60 or 65. A higher frequency of HLA-DRB1*01:01, *04:03, and *14:02 alleles and a lower frequency of HLA-DRB1*04 are observed in patients with LORA compared to young-onset RA (YORA). Due to immunosenescence, the immune response in LORA differs from that in YORA. Specifically, in LORA, there is an increase in M1 macrophages and CD56dim NK cells, whereas the numbers of M2 macrophages, Mer proto-oncogene tyrosine kinase, and CD56bright NK cells are reduced. Elevated levels of age-related B cells in older individuals may contribute to more swollen and tender joints, as well as higher disease severity scores in LORA than in YORA. Additionally, impaired DNA repair mechanisms, an increased ratio of CD4+/CD8+ T cells, and elevated CD28- T cells may contribute to a higher risk of both articular and extra-articular complications in LORA. Conventional disease-modifying antirheumatic drugs (DMARDs) used in LORA are similar to those used in YORA. Methotrexate is often the first choice for LORA; however, the dosage should be adjusted according to renal function. Biologic DMARDs is used less frequently in LORA than in YORA, as patients with LORA may be at a higher risk for serious infections. Furthermore, patients with LORA are at an increased risk of cardiovascular disease, fragility fractures, and malignancy compared to those with YORA; they also exhibit a higher prevalence of geriatric syndrome features. Furthermore, the use of antirheumatoid drugs can influence geriatric syndromes.