The role of glucagon-like peptide-1 receptor agonists (GLP1-RAs) in the management of the hypertensive patient with metabolic syndrome: a position paper from the Korean society of hypertension.

Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction.

BACKGROUND: Obesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function. METHODS: Between January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography. RESULTS: SAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r = .491, p < .001) compared to VAT (r = .371, p < .001) or EAT (r = .135, p < .001). However, EAT demonstrated the most substantial association with decreased LV end-diastolic dimension, LV end-systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p < .05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables. CONCLUSION: EAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities.

Clinical and Imaging Parameters Associated With Impaired Kidney Function in Patients With Acute Decompensated Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Acute worsening of cardiac function frequently leads to kidney dysfunction. This study aimed to identify clinical and imaging parameters associated with impaired kidney function in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF). METHODS: Data from 131 patients hospitalized with acute decompensated HFrEF (left ventricular ejection fraction, < 40%) were analyzed. Patients were divided into two groups according to the glomerular filtration rate (GFR) at admission (those with preserved kidney function [GFR ≥ 60 mL/min/1.73 m²] and those with reduced kidney function [GFR < 60 mL/min/1.73 m²]). Various echocardiographic parameters and perirenal fat thicknesses were assessed by computed tomography. RESULTS: There were 71 patients with preserved kidney function and 60 patients with reduced kidney function. Increased age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.04-1.12; p = 0.005), increased log N-terminal pro b-type natriuretic peptide (OR, 1.74; 95% CI, 1.14-2.66; p = 0.010), and increased perirenal fat thickness (OR, 1.19; 95% CI, 1.10-1.29; p < 0.001) were independently associated with reduced kidney function, even after adjusting for variable clinical and echocardiographic parameters. The optimal average perirenal fat thickness cut-off value of > 12 mm had a sensitivity of 55% and specificity of 83% for kidney dysfunction prediction. CONCLUSIONS: Thick perirenal fat was independently associated with impaired kidney function in patients hospitalized for acute decompensated HFrEF. Measurement of perirenal fat thickness may be a promising imaging marker for the detection of HFrEF patients who are more susceptible to kidney dysfunction.

Statement on chronotherapy for the treatment of hypertension: consensus document from the Korean society of hypertension.

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes.

Coffee intake and hypertension in Korean adults: results from KNHANES 2012-2016.

BACKGROUND: Coffee is the most popular and widely consumed drink in the world. Coffee consumption seems to have both benefits and risk with respect to hypertension; results from studies evaluating effect of frequency of coffee consumption on risk of hypertension are mixed and inconsistent. Hence, we investigated the association of coffee consumption and hypertension in Korean adults. METHODS: Data from Korean National Health and Nutrition Examination Survey (KNHANES) 2012-2016 was obtained and 12,133 eligible participants were selected. The coffee consumption was attained using a food frequency questionnaire. Subsequently coffee intake was grouped into two categories: ≤2 and > 2 servings per day. Hypertension status was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, use of antihypertensive drug treatment, or both. Multivariable logistic regression analysis was used to examine the association of coffee consumption and hypertension. RESULTS: Logistic regression analysis showed that consumption of more than two servings of coffee a day was inversely associated with hypertension with odds ratio (OR) 0.84 (95% confidence interval [CI], 0.73-0.99). Similar results were seen in the propensity score-matched analysis (OR, 0.83; 95% CI, 0.69-0.98). Adults having age more than median value (OR, 0.76; 95% CI, 0.65-0.89) and normal cholesterol (OR, 0.84; 95% CI, 0.70-0.99) had significantly inverse association with hypertension, when coffee consumption was more than two servings daily. CONCLUSIONS: More than two servings of coffee intake per day was inversely associated with hypertension as compared to consumption of ≤ 2 servings coffee per day.

Hounsfield Units Predict Survival of Patients With Estrogen Receptor-Positive and Human Epithelial Growth Factor Receptor 2-Negative Breast Cancer.

BACKGROUNDS: Tumor vascularity plays a fundamental role in cancer progression, including breast cancer. This study aimed to elucidate tumor vascularity and its impact on patient survival in the context of breast cancer subtypes using Hounsfield units (HU) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS: Patients with early-stage breast cancer who completed planned treatment between 2003 and 2013 were retrospectively assessed. RESULTS: The final cohort comprised 440 patients. Of the 440 patients, 262 had estrogen receptor (ER)-positive disease and 119 had human epidermal growth factor receptor 2 (HER2)-overexpressing disease. The tumor-to-aorta ratio of Hounsfield units (TAR) was related to significantly worse recurrence-free interval (RFI) (P < .001) and overall survival (OS) (P < .001) in patients with TAR > 0.33 for RFI and > 0.35 for OS than their counterparts. In the subgroup analysis, the survival disadvantage was limited only to patients with ER-positive and HER2-negative disease (P < .001 for both RFI and OS). CONCLUSION: This study showed that TAR, which reflects tumor vascularity, was significantly related to patients' RFI and OS, suggesting its capacity as a feasible biomarker. This study also showed that TAR was associated with the survival in patients with ER-positive and HER2-negative disease.

Perirenal Fat and Kidney Function Deterioration in Patients With Acute Decompensated Heart Failure.

Background and Objectives: The thick perirenal fat pad can induce high intracapsular pressure and cause compression of the renal vasculature and resultant congestive nephropathy. The current study investigated the association of perirenal fat thickness with kidney dysfunction in patients with acute decompensated heart failure (ADHF). Methods: Data from 266 patients hospitalized with ADHF were analyzed. Patients were divided into two groups according to the glomerular filtration rate (GFR) at admission (preserved kidney function [GFR ≥60 mL/min/1.73 m2] and reduced kidney function [GFR <60 mL/min/1.73 m2] groups). Right and left posterior perirenal fat thicknesses were measured using computed tomography, and their average values were calculated. Associated factors with reduced kidney function was assessed by logistic regression model, presenting with odds ratio (OR) and confidence interval (CI). Results: Increasing age (OR, 1.08; 95% CI, 1.04-1.12; p<0.001), diabetes mellitus (OR, 2.46; 95% CI, 1.18-5.12; p<0.017), increased log N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR, 1.82; 95% CI, 1.32-2.52; p<0.001), and increased average perirenal fat thickness (OR, 1.11; 95% CI, 1.06-1.16; p<0.001) were independently associated with reduced kidney function. In the subgroup analyses, patients over 70 years old, the ratio of mitral-to-mitral annular velocity >15, elevated log NT-proBNP had a significantly higher association with increased perirenal fat thickness with reduced kidney function. Conclusions: Thick perirenal fat pads were independently associated with kidney function deterioration in patients hospitalized with ADHF.

BAM15 Relieves Neurodegeneration in Aged Caenorhabditis elegans and Extends Lifespan.

BAM15 was recently screened as a protonophore uncoupler specifically for the mitochondrial membrane but not the plasma membrane. It is equally as potent as FCCP, but less toxic. Previously, mitochondrial uncoupling via DNP alleviates neurodegeneration in the nematode Caenorhabditis elegans during aging. Therefore, we investigated whether BAM15 uncouplers could phenotypically and functionally reduce neuronal defects in aged nematodes. We observed green fluorescence protein-tagged mechanosensory neurons and performed touch and chemotaxis assays during aging. Wild-type animals treated with both 50 µM BAM15 and 10 µM DNP showed reduced mechanosensory neuronal defects during aging, which correlates with the maintenance of touch responses and short-term memory during aging. Uncoupler mutant ucp-4 also responded the same way as the wild-type, reducing neurodegeneration in 50 µM BAM15 and 10 µM DNP-treated animals compared to the DMSO control. These results suggest that 50 µM BAM15 alleviates neurodegeneration phenotypically and functionally in C. elegans during aging, potentially through mitochondrial uncoupling. In accordance with the preserved neuronal shape and function in aged C. elegans, 50 µM BAM15 extended the mean lifespan of both wild-type and ucp-4 mutants.

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer.

Breast cancer is a leading cause of death worldwide. Tumor vascularity and immune disturbances are hallmarks of cancer. This study aimed to investigate the reciprocal effect of tumor vascularity, assessed by the tumor-to-aorta ratio (TAR) of Hounsfield units (HU) on computed tomography (CT), and host immunity, represented by the serum neutrophil-to-lymphocyte ratio (NLR) from peripheral, complete blood cell counts and its impact on patient survival. Female patients with breast cancer who received primary treatment between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. The final cohort included 740 patients with a mean age of 54.3 ± 11.3 (22−89) years. The TAR was 0.347 ± 0.108 (range, 0.062−1.114) and the NLR was 2.29 ± 1.53 (0.61−10.47). The cut-off value for the TAR and NLR were 0.27 and 1.61, respectively. The patients with a TAR > 0.27 showed a poor recurrence free-interval (RFI) only when their NLR was larger than 1.61, and vice versa. The patients showed worse RFI when they had both high TAR and NLR. Our results suggest a dynamic reciprocal communication between tumor vascularity and systemic immunity.

Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). METHODS: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). RESULTS: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05-1.24) but not in those by the 2017 ACC/AHA definition. Elevated on-treatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18-1.70) and stroke (aHR, 1.19; 95% CI, 1.08-1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10; 95% CI, 1.04-1.16). Similar results were seen in the propensity-score-matched cohort. CONCLUSION: Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

Angiotensin receptor-neprilysin inhibitor in patients with heart failure and chronic kidney disease.

Despite significant advances in the management of heart failure with reduced ejection fraction (HFrEF), there remains an enormous health problem with high morbidity and mortality over the last few decades. The neprilysin inhibitor enhances the activity of natriuretic peptides, producing vasodilation, natriuresis, and diuresis. Angiotensin receptor blockers inhibit the renin-angiotensin-aldosterone system. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI), has been shown to improve cardiovascular outcomes in HFrEF and delay the progression of chronic kidney disease (CKD) in patients with HFrEF. The PARADIGM-HF study showed a reduction in diuretic need in the ARNI group. While the use of diuretics is effective in volume control in patients with HFrEF, their use has the potential to adversely affect renal function. Therefore, ARNI therapy could benefit patients with heart failure and CKD by reducing cardiovascular morbidity and mortality and possibly retarding the progression of CKD, although more clinical evidence is required in patients with severe CKD and end-stage renal disease.

Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. METHODS: In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). RESULTS: In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Two-thirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. CONCLUSION: Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying high-risk patients with TNBC.

Increasing Mortality in Korean Patients With Breast Cancer: High Mortality Rate in Elderly Breast Cancer Population Due to Suboptimal Treatment and Other Diseases.

BACKGROUND: The incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival. METHODS: Patients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan-Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval. RESULTS: The final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22-89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients. CONCLUSION: Less-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.

Disparities in Mortality and Cardiovascular Events by Income and Blood Pressure Levels Among Patients With Hypertension in South Korea.

Background Socioeconomic status is associated with differences in risk factors of cardiovascular disease and increased risks of cardiovascular disease and mortality. However, it is unclear whether an association exists between cardiovascular disease and income, a common measure of socioeconomic status, among patients with hypertension. Methods and Results This population-based longitudinal study comprised 479 359 patients aged ≥19 years diagnosed with essential hypertension. Participants were categorized by income and blood pressure levels. Primary end point was all-cause and cardiovascular mortality and secondary end points were cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Low income was significantly associated with high all-cause (hazard ratio [HR], 1.26; 95% CI, 1.23-1.29, lowest versus highest income) and cardiovascular mortality (HR, 1.31; 95% CI, 1.25-1.38) as well as cardiovascular events (HR, 1.07; 95% CI, 1.05-1.10) in patients with hypertension after adjusting for age, sex, systolic blood pressure, body mass index, smoking status, alcohol consumption, physical activity, fasting glucose, total cholesterol, and the use of aspirin or statins. In each blood pressure category, low-income levels were associated with high all-cause and cardiovascular mortality and cardiovascular events. The excess risks of all-cause and cardiovascular mortality and cardiovascular events associated with uncontrolled blood pressure were more prominent in the lowest income group. Conclusions Low income and uncontrolled blood pressure are associated with increased all-cause and cardiovascular mortality and cardiovascular events in patients with hypertension. These findings suggest that income is an important aspect of social determinants of health that has an impact on cardiovascular outcomes in the care of hypertension.

Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study.

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696-0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775-0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.

Development and Validation of a Deep Learning Based Diabetes Prediction System Using a Nationwide Population-Based Cohort.

BACKGROUND: Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population. METHODS: This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve. RESULTS: During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed. CONCLUSION: The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.

Prognostic value of left atrial volume index in patients with rheumatic mitral stenosis.

BACKGROUND: The significance of left atrial volume index (LAVI) for predicting outcomes in patients with mitral stenosis (MS) has been unclear, even though rheumatic MS is known to be associated with left atrium enlargement and functional deterioration. HYPOTHESIS: The current study aimed to investigate the prognostic value of LAVI, based on the severity in patients with rheumatic MS. METHODS: We retrospectively reviewed 611 patients with pure rheumatic MS. The prognostic value of LAVI and the effect of MS severity on the prognostic value of LAVI for events were evaluated. The events were defined as a composite end-point that included all-cause death, heart failure admission, mitral valve replacement, percutaneous mitral valvuloplasty, and stroke. RESULTS: There were 236 (38.6%) overall events during a median follow-up of 8 months. The optimal LAVI cutoff for the prognostic threshold was 57 ml/m2 . The MS severity had a significant effect on the prognostic value of LAVI. A LAVI >57 ml/m2 was a prognostic value for events in progressive MS (hazard ratio [HR]: 2.40, 95% confidence interval [CI]: 1.41-5.40, p = .004) and in patients with severe MS (HR: 1.70, 95% CI: 1.06-2.74, p = .029), but it was not prognostic in patients with very severe MS (HR: 1.02, 95% CI: 0.56-1.84, p = .955). CONCLUSIONS: The prognostic value of LAVI varies and is dependent on the MS severity. A LAVI >57 mL/m2 was independently associated with poor outcomes in patients with progressive MS, while this association was minimized in patients with severe MS.

Flavonoids mitigate neurodegeneration in aged Caenorhabditis elegans by mitochondrial uncoupling.

Dietary supplementation of flavonoids has been shown to reduce the severity of neurodegenerative disorders such as dementia, Parkinson's disease, and Alzheimer's disease by their antioxidant effects. However, their low bioavailabilityin vivo raises the question of how much their antioxidant capacity actually contributes to the mitigating effects. The physicochemical properties of flavonoids suggest they could function as mitochondrial uncouplers. Moreover, mitochondrial uncoupling alleviated neurodegeneration in Caenorhabditis elegans during aging in previous research. Therefore, we investigated whether various flavonoids (fisetin, quercetin, apigenin, chrysin, catechin, and naringenin) could reduce neuronal defects by mitochondrial uncoupling in C. elegans. Both neuronal defects and mitochondrial membrane potential were reduced in aged worms in nearly all of the flavonoid treatments suggesting that flavonoids may reduce neurodegeneration in C. elegans. However, there was no significant reduction of neuronal defects in mitophagy-deficient pink-1/pdr-1 double mutants under flavonoid treatments. These results suggest that flavonoids could function as mitochondrial uncouplers to mitigate neurodegeneration in aged C. elegans, possibly via a PINK1/Parkin mitophagy process.