Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). Conclusion: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Understanding the pharmacokinetic journey of Fc-fusion protein, rhIL-7-hyFc using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA.

Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc's affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT.

Association between dementia diagnosis at dialysis initiation and mortality in older patients with end-stage kidney disease in South Korea.

Background: The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis. Methods: We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort. Results: Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization. Conclusion: A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

Relationship between Serum Total Testosterone Concentration and Metabolic Syndrome in Premenopausal Obese Women.

Background: Men with low testosterone levels are at an increased risk of developing metabolic syndrome, irrespective of age or obesity. However, the relationship between metabolic syndrome and testosterone levels in women remains unclear. We compared the total testosterone concentrations between premenopausal obese women with and without metabolic syndrome and identified the factors affecting these concentrations. Methods: A single-center retrospective analysis was conducted using the medical records of 580 premenopausal women with obesity. The diagnostic criteria for metabolic syndrome were established using the National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: The mean±standard deviation age, weight, and body mass index were 38.8±8.4 years, 78.0±11.8 kg, and 30.0±4.1 kg/m2, respectively. The mean total testosterone concentration was lower in the metabolic syndrome group than in the non-metabolic syndrome group (n=385 vs. n=195; 0.22±0.10 ng/mL vs. 0.24±0.11 ng/mL; P<0.001). In a model adjusted for age, body mass index, skeletal muscle mass, body fat mass, and body fat percentage, the odds ratio for metabolic syndrome with respect to the total testosterone level was 0.128 (P=0.028). Testosterone concentration was negatively correlated with age (r=-0.334), systolic blood pressure (r=-0.084), and triglyceride concentration (r=-0.093) but positively correlated with weight (r=0.144), body mass index (r=0.140), waist circumference (r=0.133), body fat mass (r=0.167), and body fat percentage (r=0.167). Stepwise regression analysis revealed that age (ß=-0.004, P<0.001), body mass index (ß=0.003, P=0.004), and high-density lipoprotein cholesterol concentration (ß=0.001, P=0.019) were independently associated with total testosterone concentration (adjusted R2=12.6%). Conclusion: Metabolic syndrome and obesity may be independently associated with testosterone levels in premenopausal women with obesity.

Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study.

The early mortality rate in elderly patients undergoing hemodialysis is more than twice that in young patients, requiring more specialized healthcare. We investigated whether the number of professional dialysis specialists affected early mortality in elderly patients undergoing hemodialysis. This multicenter retrospective cohort study analyzed data from 1860 patients aged ≥ 70 years who started hemodialysis between January 2010 and December 2017. Study regions included Seoul, Gyeonggi-do, Gangwon-do, Daejeon/Chungcheong-do, Daegu/Gyeongsangbuk-do, and Busan/Ulsan/Gyeongsangnam-do. The number of patients undergoing hemodialysis per dialysis specialist was calculated using registered data from each hemodialysis center. Early mortality was defined as death within 6 months of hemodialysis initiation. Gangwon-do (28.3%) and Seoul (14.5%) showed the highest and lowest early mortality rate, respectively. Similarly, Gangwon-do (64.6) and Seoul (43.9) had the highest and lowest number of patients per dialysis specialist, respectively. Relatively consistent results were observed for the regional rankings of early mortality rate and number of patients per dialysis specialist. Multivariate Cox regression analysis-adjusted for previously known significant risk factors-revealed that the number of patients per dialysis specialist was an independent risk factor for early mortality (hazard ratio: 1.031, p < 0.001). This study underscores the growing need for dialysis specialists for elderly hemodialysis patients in Korea.

Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis.

BACKGROUND: For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis. METHODS: In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs. RESULTS: DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001). CONCLUSION: Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.

A Pragmatic Randomized clinical trial: twice-weekly vs. thrice-weekly Incident hemoDialysis in Elderly patients (PRIDE): study protocol.

Background: The optimal frequency for hemodialysis in older adults with end-stage kidney disease (ESKD) has not been established. This study aims to investigate whether a twice-weekly dialysis schedule using an incremental approach can reduce hospitalization rates in the elderly with incident dialysis, compared with conventional thrice-weekly dialysis. Methods: We have designed a pragmatic randomized controlled trial to compare the effects of twice-weekly versus thrice-weekly hemodialysis in 428 ESKD individuals (dropout rate 20%) aged 60 years or older with residual kidney function (urine output, >500 mL/ day). The trial will be conducted across 18 referral hospital-based dialysis centers in Korea. Individual participants will be randomized to either a twice-weekly (with incremental approach) or thrice-weekly dialysis group and will be followed up for 24 months. The primary outcome of the study is all-cause hospitalization rate, while secondary outcomes include dialysis-specific hospitalization rates, mortality, quality of life, frailty, and cost-effectiveness. Participants have the flexibility to transfer to other dialysis centers as needed. The decision to increase dialysis frequency will be made by the treating physicians. The study is ongoing and will be completed in May 2026. Conclusion: This study will provide valuable insights into the benefits and risks of twice-weekly dialysis with an incremental approach in elderly with residual kidney function compared to thrice-weekly dialysis.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

Environmental forensics using stable and radioactive isotopes in naturally attenuated soil after phenol-leakage accidents.

Phenol is a carcinogenic and hazardous chemical used in multiple industries and poses a high risk of chemical spills into the environment. To date, environmental forensic research has not focused on chemically remediated soils. In this study, an advanced environmental forensic analysis was performed on microbial communities and breakdown products of phenol, carbon stable isotopes, and radioactive isotopes in phenol-contaminated soil. As indicators of phenol-spill accidents after natural attenuation, higher δ13C levels and lower 14C/12C ratios were observed in phenol-contaminated soil compared with uncontaminated soil. In addition, 16s rRNA gene analysis revealed that phenol-breakdown products identified by gas chromatography-mass spectrometry and the presence of soil bacteria, such as Nocardioides, Faecalibacterium, and Bacteroides, were indicators of phenol-leakage accidents. Therefore, the proposed environmental forensic strategy is a valuable tool for identifying the location of previously occurring chemical accidents and estimating the ecological impact after the natural attenuation of contaminated soils.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome.

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Verification of Therapeutic Effect through Accelerator Mass Spectrometry-Based Single Cell Level Quantification of hESC-Endothelial Cells Distributed into an Ischemic Model.

As the potential of pluripotent stem cell-derived differentiated cells has been demonstrated in regenerative medicine, differentiated vascular endothelial cells (ECs) are emerging as a therapeutic agent for the cardiovascular system. To verify the therapeutic efficacy of differentiated ECs in an ischemic model, human embryonic stem cells (hESCs) are induced as EC lineage and produce high-purity ECs through fluorescence-activated cell sorting (FACS). When hESC-ECs are transplanted into a hindlimb ischemic model, it is confirmed that blood flow and muscle regeneration are further improved by creating new blood vessels together with autologous ECs than the primary cell as cord blood endothelial progenitor cells (CB-EPCs). In addition, previously reported studies show the detection of transplanted cells engrafted in blood vessels through various tracking methods, but fail to provide accurate quantitative values over time. In this study, it is demonstrated that hESC-ECs are engrafted approximately sevenfold more than CB-EPCs by using an accelerator mass spectrometry (AMS)-based cell tracking technology that can perform quantification at the single cell level. An accurate quantification index is suggested. It has never been reported in in vivo kinetics of hESC-ECs that can act as therapeutic agents.

Chronic Inflammation as an Underlying Mechanism of Ageing and Ageing-Related Diseases.

Age-related chronic inflammation is characterized as the unresolved low-grade inflammatory process underlying the ageing process and various age-related diseases. In this chapter, we review the age-related changes in the oxidative stress-sensitive pro-inflammatory NF-κB signaling pathways causally linked with chronic inflammation during ageing based on senoinflammation schema. We describe various age-related dysregulated pro- and anti-inflammatory cytokines, chemokines, and senescence-associated secretory phenotype (SASP), and alterations of inflammasome, specialized pro-resolving lipid mediators (SPM), and autophagy as major players in the chronic inflammatory intracellular signaling network. A better understanding of the molecular, cellular, and systemic mechanisms involved in chronic inflammation in the ageing process would provide further insights into the potential anti-inflammatory strategies.

A strategy to maximize astaxanthin production from Haematococcus pluvialis in a cost-effective process by utilizing a PBR-LGP-PBR array (PLPA) hybrid system using light guide panel (LGP) and solar cells.

This study evaluated economic feasibility through production efficiency, return on investment (ROI) and payout time of a hybrid system using a photobioreactor (PBR)-light guide panel (LGP)-PBR array (PLPA) and solar cells developed for astaxanthin and ω-3 FA simultaneous production of Haematococcus pluvialis. The economic feasibility of the PLPA hybrid system (8 PBRs) and the PBR-PBR-PBR array (PPPA) system (8 PBRs) was evaluated for producing high-value products while effectively reducing CO2. Introducing a PLPA hybrid system has increased the amount of culture per area by 1.6 times. Also, the shading effect was effectively suppressed with an LGP placed between each PBR, increasing biomass and astaxanthin productivity by 3.39-fold and 4.79-fold, respectively compared to the untreated H. pluvialis cultures. In addition, ROI increased by 6.55 and 4.71 times, and the payout time was reduced by 1.34 and 1.37 times, respectively in 10 and 100-ton scale processes.

Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in TauP301L-BiFC mice.

Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer's disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. 14C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan disassembles tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents methylene blue and LMTM failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued cognitive declines induced by tauopathy in the TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.

The efficacy and safety of tadalafil in the management of erectile dysfunction with diabetes and blood circulation issues.

BACKGROUND: Erectile dysfunction (ED) is a common diabetes-related complication. MATERIALS AND METHODS: This study examined the effect of daily low-dose tadalafil (5 mg) on patients' quality of life (including that of sex life) and blood circulation. Erectile dysfunction questionnaires were administered to 20 patients with type 2 diabetes (T2DM) and ED. The safety and efficacy of tadalafil were evaluated using laboratory tests, and the effect on blood circulation was measured through nail fold capillaroscopy. RESULTS: Daily tadalafil use by patients with T2DM and ED showed a statistically significant increase in the erectile reliability score from of 1.15 to 3.20 (p < .00012). Capillary blood circulation improvement tests showed a statistically significant increase in apical limb width from 13.1 to 14.64 µm (p = .04829) and flow from 9035 to 11946 µm3/s (p = .04405). Although not significant, increased capillary width and speed (rate of blood flow) confirmed improved blood circulation. There were no significant changes in the cardiac indicators (troponin, prostate-specific antigen, or electrocardiogram tests) before and after tadalafil administration, supporting the safety of its low-dose daily administration. CONCLUSIONS: A small dose of daily tadalafil was shown to safely improve erectile dysfunction and peripheral blood flow in patients with T2DM, in which peripheral arterial diseases should not be considered separately but rather as complex entities.

Enhanced astaxanthin production of Haematococcus pluvialis strains induced salt and high light resistance with gamma irradiation.

This study was conducted to increase the productivity of biomass that contains high astaxanthin content by developing a mutant Haematococcus pluvialis strain with strong environmental tolerance. H. pluvialis has a low cell-growth rate and is vulnerable to stressors such as salinity or light intensity, which may hinder large-scale commercial cultivation. A mutant M5 strain selected through 5000-Gy gamma irradiation showed improved biomass and astaxanthin production under high-salinity and high-light intensity conditions. With enhanced SOD activity and overexpressed astaxanthin biosynthesis genes (lyc, crtR-b, bkt2), M5 demonstrated an increase in biomass and astaxanthin productivity by 86.70 % and 66.15 %, respectively compared to those of untreated cells. Also, the omega-3 content of M5 increased by 149.44 % under 40 mM CaCl2 compared to the untreated cells. Finally, even when subjected to high-intensity light irradiation for the whole life cycle, the biomass and astaxanthin concentration increased by 84.99 % and 241 %, respectively, compared to the wild-type cells.

Amyloid Against Amyloid: Dimeric Amyloid Fragment Ameliorates Cognitive Impairments by Direct Clearance of Oligomers and Plaques.

Amyloid-ß (Aß) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aß drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood-brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aß peptidomimetics that exploit the self-assembling nature of Aß and penetrate the BBB. Herein, we designed a dimeric peptide drug candidate based on the N-terminal fragment of Aß, DAB, found to cross the BBB and solubilize Aß oligomers and fibrils. Administration of DAB reduced amyloid burden in 5XFAD mice, and downregulated neuroinflammation and prevented memory impairment in the Y-maze test. Peptide mapping assays and molecular docking studies were utilized to elucidate DAB-Aß interaction. To further understand the active regions of DAB, we assessed the dissociative activity of DAB with sequence modifications.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

SMP30-mediated synthesis of vitamin C activates the liver PPARα/FGF21 axis to regulate thermogenesis in mice.

The vitamin-C-synthesizing enzyme senescent marker protein 30 (SMP30) is a cold resistance gene in Drosophila, and vitamin C concentration increases in brown adipose tissue post-cold exposure. However, the roles of SMP30 in thermogenesis are unknown. Here, we tested the molecular mechanism of thermogenesis using wild-type (WT) and vitamin C-deficient SMP30-knockout (KO) mice. SMP30-KO mice gained more weight than WT mice without a change in food intake in response to short-term high-fat diet feeding. Indirect calorimetry and cold-challenge experiments indicated that energy expenditure is lower in SMP30-KO mice, which is associated with decreased thermogenesis in adipose tissues. Therefore, SMP30-KO mice do not lose weight during cold exposure, whereas WT mice lose weight markedly. Mechanistically, the levels of serum FGF21 were notably lower in SMP30-KO mice, and vitamin C supplementation in SMP30-KO mice recovered FGF21 expression and thermogenesis, with a marked reduction in body weight during cold exposure. Further experiments revealed that vitamin C activates PPARα to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARα/FGF21 axis, contributing to the maintenance of thermogenesis in mice.