Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway.

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.

Additive Benefits of Twice Forest Bathing Trips in Elderly Patients with Chronic Heart Failure.

Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demonstrated that a 4-day forest bathing trip can provide an adjunctive therapeutic influence on patients with CHF. To further investigate the duration of the impact and the optimal frequency of forest bathing trips in patients with CHF, we recruited those subjects who had experienced the first forest bathing trip again after 4 weeks and randomly categorized them into two groups, namely, the urban control group (city) and the forest bathing group (forest). After a second 4-day forest bathing trip, we observed a steady decline in the brain natriuretic peptide levels, a biomarker of heart failure, and an attenuated inflammatory response as well as oxidative stress. Thus, this exploratory study demonstrated the additive benefits of twice forest bathing trips in elderly patients with CHF, which could further pave the way for analyzing the effects of such interventions in CVDs.

Evaluation of Environmental Risk Due to Metro System Construction in Jinan, China.

Jinan is a famous spring city in China. Construction of underground metro system may block groundwater seepage, inducing the depletion risk of springs. This paper presents an assessment of the risk due to metro line construction to groundwater in Jinan City using Analytic Hierarchy Process (AHP) and Geographic International System (GIS). Based on the characteristics of hydrogeology and engineering geology, the assessment model is established from the perspectives of surface index and underground index. The assessment results show that the high and very high risk levels of surface index exceed 98% in the north region; and high and very high risk levels of underground index exceed 56% in urban center and southern region. The assessment result also shows that about 14% of the urban area belongs to very high risk level; regions of high risk are 20% in urban area, 9% in Changqing County and 43% in Pingyin County. In the high risk region, metro lines R1 to R3, which are under construction, and metro lines L1 to L5, which are planned, have very high and high risk. Therefore, risk control measures are proposed to protect the groundwater seepage path to spring.

IFN-γ induces senescence-like characteristics in mouse bone marrow mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSC) are considered promising in tissue repair and regeneration medicine due to their proliferation and differentiation ability. Many properties of MSC are affected by cytokines, and IFN-γ has been shown to regulate MSC in many aspects. Senescence affects the proliferation, differentiation and cytokine secretion of MSC. OBJECTIVES: To investigate the effects of IFN-γ on the senescence-associated properties of MSC. MATERIAL AND METHODS: The MSC used in our study were isolated from the bone marrow (BM) of mice. Cell vitalities were measured by CCK8. The phenotypes and ROS of mBM-MSC were analyzed by flow cytometry. Cellular senescence was detected using SA-ß-gal stains. IL-6 and CXCL1 secretions were measured by ELISA. RESULTS: mBM-MSC can differentiated into osteocytes and adipocytes. They expressed CD29, CD106, and Sca-1, and did not express CD31, CD45 or FLK1. Our study showed that the cell vitalities of mBM-MSC were significantly reduced after IFN-γ treatment for 5 days, and the cell numbers were obviously lower after IFN-γ treatment for 5, 10 or 15 days. The IFN-γ group increased SA-ß-gal-positive cells and reactive oxygen species (ROS) significantly after 15 days of IFN-γ treatment. Moreover, IL-6 and CXCL1 secretions were upregulated by IFN-γ. CONCLUSIONS: Our study shows IFN-γ can induce senescence-like characteristics in mBM-MSC, suggesting a novel target for anti-aging therapy.

Health Effect of Forest Bathing Trip on Elderly Patients with Chronic Obstructive Pulmonary Disease.

Forest bathing trip is a short, leisurely visit to forest. In this study we determined the health effects of forest bathing trip on elderly patients with chronic obstructive pulmonary disease (COPD). The patients were randomly divided into two groups. One group was sent to forest, and the other was sent to an urban area as control. Flow cytometry, ELISA, and profile of mood states (POMS) evaluation were performed. In the forest group, we found a significant decrease of perforin and granzyme B expressions, accompanied by decreased levels of pro-inflammatory cytokines and stress hormones. Meanwhile, the scores in the negative subscales of POMS decreased after forest bathing trip. These results indicate that forest bathing trip has health effect on elderly COPD patients by reducing inflammation and stress level.

Downregulation of miR-146a, cyclooxygenase-2 and advanced glycation end-products in simvastatin-treated older patients with hyperlipidemia.

AIM: Hyperlipidemia is a disease with abnormally elevated levels of lipids/lipoproteins in the blood, and it is regarded as an important risk factor for cardiovascular and cerebrovascular diseases. Statins have been found to prevent vascular diseases by reducing low-density lipoprotein cholesterol and regulation of immune responses. Here, we aim to study the expression change of immune-related microRNA and genes in older patients with hyperlipidemia after treatment with simvastatin. METHODS: A total of 25 older male patients with hyperlipidemia were included in the study and received simvastatin treatment (20 mg/day). Clinical characteristics of these patients were examined, including lipoprotein cholesterol, high-sensitivity C-reactive protein, blood routine and biochemical characters. We tested miR-146a, interleukin-1-receptor-associated kinase 1, tumor necrosis factor-receptor-associated factor 6 and cyclooxygenase-2 level by real-time polymerase chain reaction, and expressions of advanced glycation end-products, p53 and p21 were analyzed by enzyme-linked immunosorbent assay. RESULTS: Simvastatin treatment effectively reduced total cholesterol and low-density lipoprotein cholesterol, but had little effect on high-density lipoprotein cholesterol. High-sensitivity C-reactive protein was slightly reduced. Expression of cyclooxygenase-2 and advanced glycation end-products were significantly reduced. Furthermore, simvastatin effectively reduced the expression of p53 and p21. Significantly downregulated miR-146a, and an obvious reduction of interleukin-1-receptor-associated kinase 1 were also detected, whereas tumor necrosis factor-receptor-associated factor 6 remained unchanged. Besides, there was a significant reduction of alanine transaminase, aspertate aminotransferase, alkaline phosphatase and lactate dehydrogenase. CONCLUSION: Simvastatin treatment could inhibit inflammation and senescence-associated genes in older patients with hyperlipidemia, suggesting its application in inflammatory and age-related diseases.

Therapeutic effect of forest bathing on human hypertension in the elderly.

OBJECTIVE: To provide scientific evidence supporting the efficacy of forest bathing as a natural therapy for human hypertension. METHODS: Twenty-four elderly patients with essential hypertension were randomly divided into two groups of 12. One group was sent to a broad-leaved evergreen forest to experience a 7-day/7-night trip, and the other was sent to a city area in Hangzhou for control. Blood pressure indicators, cardiovascular disease-related pathological factors including endothelin-1, homocysteine, renin, angiotensinogen, angiotensin II, angiotensin II type 1 receptor, angiotensin II type 2 receptor as well as inflammatory cytokines interleukin-6 and tumor necrosis factor α were detected. Meanwhile, profile of mood states (POMS) evaluation was used to assess the change of mood state of subjects. In addition, the air quality in the two experimental sites was monitored during the 7-day duration, simultaneously. RESULTS: The baselines of the indicators of the subjects were not significantly different. Little alteration in the detected indicators in the city group was observed after the experiment. While subjects exposed to the forest environment showed a significant reduction in blood pressure in comparison to that of the city group. The values for the bio-indicators in subjects exposed to the forest environment were also lower than those in the urban control group and the baseline levels of themselves. POMS evaluation showed that the scores in the negative subscales were lowered after exposure to the forest environment. Besides, the air quality in the forest environment was much better than that of the urban area evidenced by the quantitative detection of negative ions and PM10 (particulate matter < 10 µm in aerodynamic diameter). CONCLUSION: Our results provided direct evidence that forest bathing has therapeutic effects on human hypertension and induces inhibition of the renin-angiotensin system and inflammation, and thus inspiring its preventive efficacy against cardiovascular disorders.

Effects of short-term forest bathing on human health in a broad-leaved evergreen forest in Zhejiang Province, China.

OBJECTIVE: To investigate the effects of short-term forest bathing on human health. METHODS: Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states. RESULTS: No significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased. CONCLUSION: Forest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.

Antiaging effect of pine pollen in human diploid fibroblasts and in a mouse model induced by D-galactose.

The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL) is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-ß-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21(Waf1), p16(INK4a), PTEN, and p27(Kip1) in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts) formation inhibitor aminoguanidine (AG), pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG) in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.

[Estimation of spike wave reduction in electrocorticography for predicting the outcomes of epilepsy surgery].

OBJECTIVE: To investigate spike wave reduction in electrocorticography (EcoG) monitoring for evaluating the outcomes of epilepsy surgery. METHODS: The epileptogenesis lesions in the target cortex was localized accurately using an EcoG monitoring system in 20 surgical patients with intractable EP. The spike numbers within 60 s were recorded before and after surgical resection of the epileptogenic focus. In cases where the spike number within 60 s was reduced by over 80% after the resection, the surgery was terminated, otherwise extended lesion resection, corpus callosotomy or multiple subpial transection (MST) was carried out with ECoG monitoring, and the spike number within 60 s was recorded. Antiepileptic drugs were routinely prescribed after the operations. RESULTS: Twelve patients exhibited a spike wave reduction by over 80% after resection or extended resection of the lesions, including 4 with cavernomas in the nonfunctional area, who showed a spike wave reduction by over 80% after extended resection of the cortex around the tumor. The reduction was still less than 80% in 4 patients with hippocampal sclerosis and 3 with neurogliocytoma in the functional area after the operations. According to the Engel assessments, 13 cases were in level I, 3 cases in level II, 1 in level III, and 3 in level IV. Seventeen patients responded favorably to the treatment, with a total effective rate of 85%. CONCLUSION: For extra-temporal lobe epilepsy, a postoperative spike wave reduction beyond 80% indicate favorable outcome of the surgery, otherwise poor prognosis is expected. But in cases of temporal lobe epilepsy, no direct association is found between spike wave reduction and the prognosis of the patients.

[Clinical observation on catgut implantation at acupoint for treatment of somatic form disorders].

OBJECTIVE: To compare therapeutic effects of catgut implantation at acupoint plus small dose of Paroxetine Hydrochloride and simple Paroxetine Hydrochloride. METHODS: Eighty-eight cases of such disease were divided into 2 groups, a treatment group (n=54) and a control group (n=34). The treatment group were treated with catgut implantation at main points Dazhui (GV 14), Zhongwan (CV 12), Tianshu (ST 25), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), etc., plus oral administration of small dose of Paroxetine Hydrochloride; and the control group were treated with simple Paroxetine Hydrochloride. They were treated for 6 weeks. Hamilton Depression Rating Scale (HAMD) was used for assessment of the therapeutic effect. RESULTS: The effective rate was 92.6% in the treatment group and 85.3% in the control group with a significant difference between the two groups (P < 0.05); at the end of the first week and the second week of treatment, the score for HAMD in the treatment group significantly decreased as compared with that in the control group (P < 0.01). CONCLUSION: Catgut implantation at acupoint plus small dose of Paroxetine Hydrochloride has a better therapeutic effect on somatic form disorders.