Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
Humans ; Medicine, Chinese Traditional ; Neurodegenerative Diseases/drug therapy* ; Brain ; Aging ; Neurons ; Blood-Brain Barrier

Objective: To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA). Methods: This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants' characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values. Results: The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24). Conclusion: The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.
Aging ; Ankle Brachial Index ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cardiovascular Physiological Phenomena ; Cross-Sectional Studies ; Humans ; Pulse Wave Analysis ; Risk Factors

Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
Aging ; Angiotensin II ; Animals ; Aorta/physiopathology* ; Blood Pressure/genetics* ; Gene Expression Profiling/methods* ; Gene Ontology ; Hypertension/genetics* ; Male ; Mice, Inbred C57BL ; Reverse Transcriptase Polymerase Chain Reaction

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence-associated β-galactosidase (SA-β-gal) activity. Tenovin-1-treated astrocytes showed increased SA-β-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-1β, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.
Aging ; Animals ; Astrocytes ; Blood-Brain Barrier ; Brain ; Cell Aging ; Cell Count ; Cell Cycle Checkpoints ; Interleukin-6 ; Language ; Memory ; Neurodegenerative Diseases ; Neurons ; Permeability ; Phenotype ; Rats ; Wound Healing

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer’s disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.
Aging ; Amyotrophic Lateral Sclerosis ; Atherosclerosis ; Blood Circulation ; Blood-Brain Barrier ; Brain ; Cholesterol ; Metabolism ; Mitochondria ; Neurodegenerative Diseases ; Parkinson Disease

The increasing risk of glucose intolerance and diabetes associated with aging is well established. However, it is difficult to determine whether changes in glucose metabolism result from biological aging itself or due to various environmental factors that occur during the aging process. Many epidemiologic studies have shown that plasma glucose levels after oral glucose tolerance test rise consecutively for every decade of age, but many of these studies also demonstrated the effects of environmental factors including obesity and exercise. In some studies, the development of insulin resistance and insulin secretion defects due to biological aging itself have also been identified as major etiologic factors of glucose intolerance. However, the rate of diabetes development due to these factors is expected to be very slow and largely preventable by addressing environmental risk factors.
Aging ; Blood Glucose ; Carbohydrate Metabolism ; Epidemiologic Studies ; Glucose Intolerance ; Glucose Tolerance Test ; Glucose ; Incretins ; Insulin ; Insulin Resistance ; Metabolism ; Obesity ; Risk Factors

OBJECTIVE: This study aimed to evaluate the prognostic impact of age at diagnosis, and pretreatment hematologic markers, including lymphocyte percentage and the neutrophil-to-lymphocyte ratio (NLR), in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy (RT). METHODS: A total of 392 patients with LACC (stage IIb to IVa) treated with cisplatin-based concurrent chemoradiotherapy or RT alone between 2001 and 2012 were retrospectively enrolled. Clinical data and pretreatment complete blood counts were extracted from electronic medical records of the patients, and analyzed. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Low lymphocyte percentage and a high NLR were associated with younger age, advanced stage, larger tumor size, lymph nodes metastasis, and treatment failure. The cut-off value for lymphocyte percentage and NLR was determined using a receiver operating characteristic curve. In univariate analysis, low lymphocyte percentage (≤24%) was associated with poor PFS and OS, while high NLR ( > 2.8) was significantly associated only with PFS. In multivariate analysis, both lymphocyte percentage (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40–0.85; P=0.005) and NLR (HR, 1.55; 95% CI, 1.07–2.25; P=0.022) had independent prognostic value for PFS. Compared to younger patients (age ≤50 years), older patients (age > 60 years) had a lower risk of death. CONCLUSION: Although the lymphocyte percentage did not remain significant in multivariate analysis for OS, it was predictive of PFS and OS. Thus, lymphocyte percentage is a simple hematologic parameter with a significant prognostic value in patients with LACC treated with definitive RT.
Aging ; Blood Cell Count ; Chemoradiotherapy ; Diagnosis* ; Disease-Free Survival ; Electronic Health Records ; Hematologic Tests ; Humans ; Lymph Nodes ; Lymphocytes* ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Radiotherapy* ; Retrospective Studies ; ROC Curve ; Treatment Failure ; Uterine Cervical Neoplasms*

BACKGROUND: The incidence of cardiovascular and neurovascular diseases has been increasing with the aging of the population, and antiplatelet drugs (APDs) are more frequently used than in the past. With the average age of spinal surgery patients also increasing, there has been a great concern on the adverse effects of APD on spine surgery. To our knowledge, though there have been many studies on this issue, their results are conflicting. In this study, we aimed to determine the influence of APDs on spine surgery in terms of intraoperative bleeding and postoperative spinal epidural hematoma complication. METHODS: Patients who underwent posterior thoracolumbar decompression and instrumentation at our institution were reviewed. There were 34 APD takers (APDT group). Seventy-nine non-APD takers (NAPDT group) were selected as a control group in consideration of demographic and surgical factors. There were two primary endpoints of this study: the amount of bleeding per 10 minutes and cauda equina compression by epidural hematoma measured at the cross-sectional area of the thecal sac in the maximal compression site on the axial T2 magnetic resonance imaging scans taken on day 7. RESULTS: Both groups were homogeneous regarding age and sex (demographic factors), the number of fused segments, operation time, and primary/revision operation (surgical factors), and the number of platelets, prothrombin time, and activated partial thromboplastin time (coagulation-related factors). However, the platelet function analysis-epinephrine was delayed in the APDT group than in the NAPDT group (203.6 seconds vs. 170.0 seconds, p = 0.050). Intraoperative bleeding per 10 minutes was 40.6 ± 12.8 mL in the APDT group and 43.9 ± 9.9 mL in the NAPDT group, showing no significant difference between the two groups (p = 0.154). The cross-sectional area of the thecal sac at the maximal compression site by epidural hematoma was 120.2 ± 48.2 mm2 in the APDT group and 123.2 ± 50.4 mm2 in the NAPDT group, showing no significant difference between the two groups (p = 0.766). CONCLUSIONS: APD medication did not increase intraoperative bleeding and postoperative spinal epidural hematoma. Therefore, it would be safer to perform spinal surgery without discontinuation of APD therapy in patients who are vulnerable to cardiovascular and neurovascular complications.
Aging ; Blood Platelets ; Cauda Equina ; Decompression ; Hematoma ; Hematoma, Epidural, Spinal ; Hemorrhage ; Humans ; Incidence ; Magnetic Resonance Imaging ; Partial Thromboplastin Time ; Platelet Aggregation Inhibitors ; Prothrombin Time ; Spine*

BACKGROUND: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 10/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.
Aged ; Aged, 80 and over ; Aging ; blood ; physiology ; Carotid Artery Diseases ; blood ; physiopathology ; Carotid Intima-Media Thickness ; Confidence Intervals ; Cross-Sectional Studies ; Humans ; Hypertension ; blood ; physiopathology ; Japan ; Male ; Middle Aged ; Odds Ratio ; Platelet Count ; Pressure ; Risk Factors ; Tongue ; physiology

BACKGROUND: Age-related musculoskeletal diseases are becoming increasingly burdensome in terms of both individual quality of life and medical cost. We intended to establish a large population-based cohort study to determine environmental, lifestyle, and genetic risk factors of musculoskeletal and other age-related diseases, and to clarify the association between vitamin D status and such diseases. METHODS: We targeted 34,802 residents aged 40-74 years living in areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura Village, and Murakami City (Murakami region). The baseline questionnaire survey, conducted between 2011 and 2013, queried respondents on their lifestyle and environmental factors (predictors), and self-reported outcomes. Plasma 25-hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was determined with the Liaison® 25OH Vitamin D Total Assay. The primary outcome of this study was osteoporotic fracture; other outcomes included age-related diseases including knee osteoarthritis, perception of chronic pain, dementia, and long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N = 6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD = 18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively. DISCUSSION Follow-up surveys are planned every 5 years for 15 years, and incident cases of our targeted diseases will be followed at hospitals and clinics in and nearby the cohort area. We anticipate that we will be able to clarify the association between vitamin D status and multiple disease outcomes in a Japanese population.
Aged ; Aging ; Cohort Studies ; Epidemiologic Research Design ; Female ; Humans ; Incidence ; Japan ; epidemiology ; Male ; Middle Aged ; Musculoskeletal Diseases ; epidemiology ; prevention & control ; Predictive Value of Tests ; Quality of Life ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood