Dataset for life cycle assessment of strawberry-package supply chain with considering food loss during transportation.

This dataset includes two kinds of data (for inventory analysis in Table A1 to A13, and precondition of waste and recycle for plastic and cardboard in Table A14) for conducting life cycle assessment (LCA) of strawberry-package supply chain with considering food loss during transportation Inventory analysis includes input data for LCA analysis. The data in the inventory was referenced from the publication of Plastic Waste Management Institute Plastic Waste Management Institute, (2017) and calculated based on the damage area ratio measured in our co-submitted article (Sasaki et al., 2022). This data helps to reproduce the article (Sasaki et al., 2022) for inventory analysis and re-analyze the environmental impact through the life cycle of strawberry assessed in the co-submitted article. Data of waste (incineration and landfill) and recycle ratios for plastic was collected from the previous reports of the publication Basic Knowledge of Plastic Recycle 2021 (Plastic Waste Management Institute, 2021), and data of the ratios for cardboard was referenced from Transition of Collect Rate on Cardboard (Ministry of the Environment (MOE), 2016). Ratios in this data show Japan-specialized values and is useful for creating the inventory.

Chromosomal terminal methylation status is associated with gut microbiotic alterations.

We explored the association of fecal bacterial species and somatic telomere changes in patients with chronic disease. The results showed that the length of the combined range of telomere and the methylated subtelomere was correlated with the increase of bacteria species and the numerical superiority of certain strains in feces, the increase of streptococci in men and women, and the increase of E. coli specifically in women. These results suggest that the aging status reflected by telomere length and/or demethylation of neighboring regions correlate with intestinal conditions which influences the proportion of the intestinal microbial population. Shortened telomere length and subtelomeric demethylation status are thought to represent the degree of aging and the accelerating stage of aging velocity, respectively. Hence, the observed biased microbial status is considered to be associated with advanced stage or acceleration phase of biological aging.

Telomere shortening velocity of patients administered with hypnotics is accelerated in a gender-differential manner.

The telomere length and its distribution were compared between patients administered with and without hypnotics to see if regular administration of hypnotics is associated with their aging-related somatic telomere shortening. Male patients presented significant shortening of telomere length of circulating leukocytes in association with age (-41.9 bp/year, p = 0.045) in contrast with controls (-18.3 kb/year, p = 0.155). On the other hand, female patients presented no significant shortening of telomere length with aging (-16.4 bp/year, p = 0.372) in contrast with controls (-55.9 bp/year, p = 0.00005). These results suggested that regular administration of hypnotics is associated with aging progression in a gender-related manner. The administration of hypnotics could be an indicator as the somatic aging status and for the screening of background lifestyle-associated diseases promoting biological aging.

Calorie restriction delays cardiac senescence and improves cardiac function in obese diabetic rats.

The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac senescence in an animal model of diabetes and examine the signal transduction mechanisms for changes in cell survival as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into 2 groups: a group fed ad libitum (AL), and a group fed with CR (30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were divided into 3 groups: a high fat diet (HFD) group with a 22% increase in caloric intake, a CR group, and a group fed AL. At 40 weeks of age, the telomere length was significantly shorter in the heart tissue of HFD rats but was not altered by CR in experimental rats with or without CR, however, telomerase activity in both strains of CR rats was significantly elevated. Protein expression of IGF-1, Sirt 1 and phospho-FoxO1 was increased in both CR groups. Echocardiography showed that CR preserved LV diastolic function with a significantly shorter E-wave deceleration time and a greater E/A ratio compared with the AL groups. These findings suggest that CR protocol increased telomerase activity without changing of telomere length, enhanced autophagy and improved LV diastolic function in animal model of diabetes rats. It is finally suggested that those impacts may be important for the maintenance of normal cardiac function and for delayed cardiac aging.

The approximate formulas predicting personal somatic telomere length using patient blood test data.

Biological aging underlies lifestyle-related diseases. It can be assessed by measuring personal somatic cell telomere length. However, measuring the telomere length is laborious, and its clinical surrogate parameters have not been developed. This study analyzed the correlation between telomere length in peripheral leukocytes and laboratory data to select test items relating closely to biological aging. We established formulas from these clinical data to predict the personal telomere length. The subjects were patients having visited Kyushu University Beppu Hospital from 2012 to 2015. Two hundred and thirty-two patients were enrolled. The blood data were collected and telomere lengths were measured by Southern blotting method. The patients showed significant correlations between the telomere length and several blood test data with a sex-related difference. Candidate formulas are as follows: Predicted telomere length (kb) in men = 8.59 - 0.037 × Age (years) + 0.024 × Hemoglobin (g/dL); Predicted telomere length (kb) in women = 4.83 - 0.019 × Age (years) + 0.23 × Albumin (g/dL) + 0.0001 × White blood cells (/mm3) + 0.0020 × Red blood cells (× 104/mm3) + 0.0032 × Total cholesterol (mg/dL). Thus, the derived formulas allow for the accurate differential prediction of telomeric length in male and female patients.

Short telomere subtelomeric hypomethylation is associated with telomere attrition in elderly diabetic patients 1.

Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes (T2D) patients and diabetes-free controls (C). The methylation status was analyzed between MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. The mean telomere lengths, MspI-TRF or HpaII-TRF, were not significantly different between C and T2D patients. The percentage of fractionated densitometry showed that long and middle telomeres (>9.4 kb, 4.4-9.4 kb) were unaltered but short telomeres (<4.4 kb) in T2D patients were increased compared with C group. The methylation status revealed subtelomeric hypomethylation in short telomeres of T2D patients. When some patients with T2D were treated with 3-hydroxy-3-methylglutaril coenzyme A (HMG-CoA) reductase inhibitors (statin), results seen in short telomere of T2D patients were not observed and were not different from C. This suggested that this altered subtelomeric hypomethylation may be associated with the accelerated telomere shortening in elderly diabetic patients. These results also mean that the subtelomeric hypomethylation can also be influenced by statin treatment in T2D.

Shorter somatic telomere can be an increased risk for hospitalization.

Somatic telomere DNA length is known to shorten with certain disease states and senescence. Furthermore, we have reported that the telomere length of a sub-healthy population also correlates with the blood data of laboratory tests. These facts suggest that patients with shorter telomere length tend to be hospitalized more easily than patients with longer telomere length. And such hospitalization tendencies can also be reflected in differences in clinical laboratory data. To address this issue, we evaluated and compared the telomere length and clinical laboratory data of outpatients and inpatients. In this study, 35 inpatients with chronic illness and 38 outpatients with one or more weeks without hospitalization experience were enrolled. Telomere length was shorter in hospitalized patients than outpatients. Inpatients and outpatients showed significant differences in some laboratory test results. Male outpatients showed higher values of fast blood sugar, HbA1c, blood urea nitrogen, creatinine, C-reactive protein, red blood cell count, and hemoglobin. Among female outpatients, the values of aspartate aminotransferase, alanine aminotransferase, albumin, creatine kinase, red blood cell count and hemoglobin were high. Of these, only albumin levels showed a positive correlation with telomere length in both sexes. Unexpectedly, all the other clinical data distinguishing outpatients and inpatients showed no significant association with telomere length. These items appeared to be related to hospital risk independently of TL. Having a shorter somatic telomere length appeared to be at a higher risk of hospitalization. This risk can be augmented by further complications such as deterioration of nutritional status and anemia. Maintaining sufficiently high nutritional status and erythropoietic potential may lead to avoidance of clinical events that require hospitalization.

Sarcolemmal Alterations in Unloaded Rat Heart after Heterotopic Transplantation.

Following heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca 2+ transients. Furthermore, the sarcoplasmic reticular Ca 2+ uptake and release activities were reduced and Ca 2+ influx through L-type Ca 2+ channels was increased in the atrophied heart. Since Ca 2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca 2+ concentration, the present study was undertaken to test if sarcolemma plays any role to maintain cardiac function in the atrophied heart.The characteristics of sarcolemmal Ca 2+ pump and Na + -Ca 2+ exchange activities were examined in 8 weeks heterotopically isotransplanted rat hearts which did not support hemodynamic load and underwent atrophy. Sarcolemmal ATP (adenosine triphosphate)-dependent Ca 2+ uptake and Ca 2+ -stimulated ATPase (adenosine triphosphatase) activities were increased without any changes in Na + -K + ATPase activities in the transplanted hearts. Although no alterations in the Na + -dependent Ca 2+ uptake were evident, Na + -induced Ca 2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na + -induced Ca 2+ release was observed at different times of incubation as well as at 5, 20, and 40 mM Na + . The sarcolemma from transplanted hearts also showed higher contents of phosphatidic acid, sphingomyelin, and cholesterol.These results indicate that increases in the sarcolemmal, Ca 2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.

Epigenetic status of subtelomere of peripheral leukocytes corresponds to cardiographic parameters with a sex association.

AIM: The telomere length of somatic cells is associated with systemic aging. The attrition of somatic telomere length is accelerated in pathological conditions, such as cardiovascular diseases. However, clinical parameters of cardiac function have not been well studied in this regard. The present study examined how cardiac function was affected by telomere length and the subtelomeric methylation of peripheral leukocytes. METHODS: Telomere length was assessed by Southern blotting analysis of genomic DNA extracted from peripheral leukocytes. Subtelomeric methylation was assessed by comparison between the Southern blotting results with a restriction enzyme Msp I and those with Hpa II, a methylation-sensitive isoschizomer of Msp I. RESULTS: The following parameters were associated with telomere length and/or the subtelomeric methylation status in a sex-associated manner: PR interval, the voltage of QRS complex, QRS interval, QT interval and T wave voltage in electrocardiogram; and ejection fraction, the diameter of the left ventricle at the end diastolic phase, aortic root diameter and inferior vena cava diameter in echocardiogram. CONCLUSIONS: Cardiac function correlates not only with telomere length, but also with the distribution of the telomere length and subtelomeric DNA methylation status. These imply that the loss of young cells, the accumulation of old cells and the acceleration of such changes in the cell population relate to phenotypes of cardiac aging with relative sex specificity. Furthermore, the PR interval showed a very close association with telomeric parameters in both sexes. Hence, PR is the most reliable candidate as an indicator of biological aging in both sexes. Geriatr Gerontol Int 2018; 18: 1415-1419.

Preventive and promotive effects of habitual hot spa-bathing on the elderly in Japan.

Although body-warming with hot spa-bathing has been proposed to exert medical therapeutic effects on certain diseases, whether body-warming has preventive and promotive effects remains unknown. To clarify this issue, an epidemiological questionnaire study regarding personal hot spa-bathing habits and disease history was carried out in Japan, where individuals engage in daily warm water bathing. Questionnaires regarding hot spa-bathing habits and disease history were randomly sent to 20,000 residents aged ≥65 years living in Beppu, a city in Japan that has the highest concentration of hot spa sources in the world. The results showed that habitual hot spa-bathing exerts preventive or promotive effects on the occurrence of certain diseases, such as hypertension (preventive) and collagen disease (promotive) in women, and cardiovascular diseases (preventive) and colon cancer survival (promotive) in men. These findings suggest that habitual body warming is an effective and economical method with beneficial preventive and promotive effects on various diseases.

Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia.

Spa bathing is known as a medical treatment for certain diseases causing chronic pains. Spa water contains mineral components which lower the specific heat of the water, resulting in a higher efficiency to warm body-core temperature. This phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain, sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the changes of blood examination data, and the telomere length of circulating leukocytes. The enrolled 7 patients with fibromyalgia syndrome were hospitalized and were subject to daily mud bathing at 40 °C for 10 min for about a month. Then, their subjective pain was reduced to about a quarter in average. They also showed lowered serum triglyceride and C-reactive protein level, maintaining the levels of aspartate transaminase and creatine phosphokinase, and increases of the red blood cell count, the serum albumin level, and the serum LDL-cholesterol level in comparison with cases without mud-bathing therapy, suggesting that mud bathing prevents inflammation and muscle atrophy and improves nutritional condition in fibromyalgia. In addition, the analysis of telomere length of peripheral leukocytes revealed a trend of negative correlation between telomere shortening and laboratory data change of hemoglobin and serum albumin. These telomeric changes can be explained hypothetically by an effect of mud bathing extending life-span of circulating leukocytes.

EGCG, a green tea catechin, attenuates the progression of heart failure induced by the heart/muscle-specific deletion of MnSOD in mice.

BACKGROUND: Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme affected in heart/muscle-specific MnSOD-deficient mice (H/M-SOD2-/-), which develop progressive congestive heart failure and exhibit pathology typical of dilated cardiomyopathy. METHODS: In this study we investigated the beneficial effects of epigallocatechin gallate (EGCG) on the cardiac remodeling and telomere biology in H/M-SOD2-/- mice. H/M-SOD2-/- mice were divided into three groups: those receiving normal drinking water (KO), a low dose of EGCG (L: 10mg/L), and a high dose of EGCG (H: 100mg/L) beginning at eight weeks of age and lasting for eight weeks. RESULTS: The mice in the KO group exhibited significantly dilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although the mortality of KO mice was about 50% at 16 weeks of age, the mice that received EGCG had a high survival rate. The cardiac dilatation with reduced cardiac contraction in KO mice was prevented by EGCG treatment. The levels of myocardial oxidative stress and free fatty acids were lower in the group treated with EGCG compared with the KO group. The increased expression of nitric oxide synthase 2, nitrotyrosine, fatty acid synthase, Toll-like receptor 4, and Sirt1 in the KO mice were prevented by EGCG treatment. The shortening of the telomere length, decreased telomerase activity in KO mice were also prevented by EGCG. CONCLUSIONS: H/M-SOD2-/- mice receiving EGCG have a lower mortality rate and exhibit less inflammation and a better preserved cardiac function and telomere biology.

[Intra-operative Acute Aortic Dissection during Aortic Root Reimplantation and Mitral Valve Reconstruction Surgery in a Patient with Marfan Syndrome;Report of a Case].

In patients with Marfan syndrome, cardiovascular complication due to aortic dissection represents the primary cause of death. Iatrogenic acute aortic dissection during cardiac surgery is a rare, but serious adverse event. A 51-year-old woman with Marfan syndrome underwent elective aortic surgery and mitral valve reconstruction surgery for the enlarged aortic root and severe mitral regurgitation. We replaced the aortic root and ascending aorta based on reimplantation technique. During subsequent mitral valve reconstruction, we found the heart pushed up from behind. Trans-esophageal echocardiography revealed a dissecting flap in the thoracic descending aorta. There was just weak signal of blood flow in the pseudolumen. We did not add any additional procedures such as an arch replacement. Cardio-pulmonary bypass was successfully discontinued. After protamine sulfate administration and blood transfusion, blood flow in the pseudolumen disappeared. The patient was successfully discharged from the hospital on 33th postoperative day without significant morbidities.

Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts.

The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7% and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening.

Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2α concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2α in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.

Altered expression of genes associated with telomere maintenance and cell function of human vascular endothelial cell at elevated temperature.

The pathophysiological alterations of vascular endothelial cells induced by heat were studied. Human umbilical venous endothelial cells were cultured for 1 day at three different temperatures (37, 39, and 42 °C). The telomere lengths, the expressions of proteins associated with telomere length maintenance, apoptosis, heat shock, and vascular function were analyzed. The cell growth was not suppressed at 39 °C but suppressed at 42 °C. The mean telomere length did not change, whereas the telomere length distribution altered at 42 °C. Long telomere decreased and middle-sized telomere increased in the telomere length distribution at 42 °C. The telomerase activity did not show any heat-associated alterations. However, of the components of telomerase, telomerase reverse transcriptase was up-regulated along temperature elevation. In contrast, the expression level of RNA component TERC did not altered. Among the analyzed apoptosis-associated proteins, p21 was down-regulated and phosphorylated p53 was up-regulated. Heat shock proteins and NO synthase were up-regulated at 42 °C. These results suggested that induced growth suppression or cell senescence was induced by strong heat stress rather than mild one predominantly in cells bearing long telomeres with p53 activation, and simultaneously activated some telomere-associated factors, heat shock proteins, and NO synthesis probably for heat-resistant cell survival.

Changes in telomere length distribution in low-dose X-ray-irradiated human umbilical vein endothelial cells.

Ionizing radiation (IR) is known to be a cause of telomere dysfunction in tumor cells; however, very few studies have investigated X-ray-related changes in telomere length and the telomerase activity in normal human cells, such as umbilical vein endothelial cells (HUVECs). The loss of a few hundred base pairs from a shortened telomere has been shown to be important with respect to cellular senescence, although it may not be detected according to traditional mean telomere length [assessed as the terminal restriction fragment (TRF)] analyses. In the present study, a continuous time window from irradiation was selected to examine changes in the telomere length, including the mean TRF length, percentage of the telomere length, telomerase activity, apoptotic rate, and survival rate in HUVECs from the first day to the fourth day after the administration of a 0.5-Gy dose of irradiation. The mean TRF length in the irradiated HUVECs showed shorter telomere length in first 3 days, but they were not statistically significant. On the other hand, according to the percentage analysis of the telomere length, a decreasing tendency was noted in the longer telomere lengths (9.4-4.4 kb), with a significant increase in the shortest telomeres (4.4-2.3 kb) among the irradiated cells versus the controls from the first day to the third after irradiation; no significant differences were noted on the fourth day. These results suggest that the shortest telomeres are sensitive to the late stage of radiation damage. The proliferation of irradiated cells was suppressed after IR in contrast to the non-irradiated cells. The apoptotic rate was elevated initially both in IR- and non-IR-cells, but that of IR-cells was maintained at an elevated level thereafter in contrast to that of non-IR-cells decreasing promptly. Therefore, a 0.5-Gy dose of IR induces persistent apoptosis leading to an apparent growth arrest of the normal HUVECs.

Alterations in the telomere length distribution and the subtelomeric methylation status in human vascular endothelial cells under elevated temperature in culture condition.

Temperature-associated alteration in the telomere lengths of vascular endothelial cells has not been well investigated. Telomere length of human umbilical vein endothelial cells (HUVECs) cultured at a high temperature (42 °C) was analyzed. Here described are heat-associated phenotypical alterations of human vascular endothelial cell under prolonged heat stress in terms of telomere length, telomerase activity, and the expression of telomere associated proteins and heat shock proteins. The genomic DNA extracted from HUVECs cultured for 3 days under 42 °C was digested with methylation-sensitive and -insensitive isoschizomers and was subjected to genomic Southern blot probed with a telomere DNA fragment. Their telomere lengths and telomere length distributions were analyzed. Telomerase activity and the expressions of telomere-associated RNA, telomere-associated proteins (TERC, TERT, TRF1, and TRF2), and heat shock proteins (Hsp60, Hsp70, and Hsp90) were also analyzed. At 42 °C, cell growth was suppressed and the cell senescence rate was transiently elevated. A proportional decrease in the number of long telomeres was observed transiently at 42 °C. A trend of subtelomeric hypomethylation and lowered telomerase activity were observed at 42 °C after 3-day culture. The altered phenotypes on day 1 seemed reactive responses for cell protection to heat, and those on day 3 seemed exhausted reactions after 3-day culture. Maintained expression was observed in Hsps, TRF2, and TERC. These altered phenotypes might contribute to cell-survival under prolonged heat stress.

Analysis of telomere length and subtelomeric methylation of circulating leukocytes in women with Alzheimer's disease.

BACKGROUNDS AND AIMS: Telomere attrition proceeds with the aging process, and is also associated with aging disease conditions, such as Alzheimer's disease (AD). The aging process also affects subtelomeric methylation status. In the present study, the telomere length and the subtelomeric methylation status in female AD patients were analyzed to see how AD affects telomere structure. METHODS: Terminal restriction fragment length of 23 AD patients' peripheral leukocytes was analyzed with methylation sensitive- and insensitive-isoschizomer by Southern blot. RESULTS: AD patients were found to have normal mean telomere lengths (controls; 6.4 ± 0.9 kb, AD; 6.1 ± 0.8 kb, p = 0.131), a proportionally decreased number of the longest telomeres (>9.4 kb) (controls; 30.3 ± 7.9%, AD; 24.4 ± 8.3%, p = 0.013), increased medium-sized telomeres (controls; 51.7 ± 3.3%, AD 55.5 ± 6.4%, p = 0.015) and unchanged numbers of the shortest telomeres (<4.4 kb) (controls; 18.0 ± 7.8, AD; 20.2 ± 8.9%, p = 0.371) in their peripheral leukocytes. The subtelomeres of telomeres in the shortest range (<4.4 kb) were more methylated in AD subjects than in controls (controls; 0.21 ± 0.23, AD; 0.41 ± 0.26, p = 0.016). CONCLUSIONS: These results may indicate that AD contributes to the loss of cells bearing the shortest telomeres, with hypomethylation of subtelomeres occurring in addition to telomere attrition, resulting in an apparent normal mean telomere length in AD patients. The relatively high subtelomeric methylation status of the shortest telomeres in peripheral blood leukocytes may be a characteristic of AD. This report demonstrates that the epigenetic status of the telomeric region is affected by disease conditions.

Hyperthermia by bathing in a hot spring improves cardiovascular functions and reduces the production of inflammatory cytokines in patients with chronic heart failure.

Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF). Thirty-two patients with systolic CHF classified as New York Heart Association functional status II or III were randomized to divide either a balneotherapy group or a control group. The patients in the balneotherapy group were immersed in a hot spring at 40°C for 10 min daily for 2 weeks; the control group patients took a shower daily. The left ventricular ejection fraction (EF) and cardiothoracic ratio (CTR) were evaluated and plasma brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels were measured. The clinical symptoms improved after 2 weeks of hot spring therapy. Although the heart rate did not change, clinical symptoms, CTR, EF, and BNP were significantly improved. Moreover, the inflammatory responses, including hsCRP, TNF-α and IL-6 decreased significantly after balneotherapy. The improvement of BNP correlates with the changes in inflammatory biomarkers. Repeated hyperthermia by bathing in a hot spring is therefore considered to improve the cardiac and inflammatory status in patients with CHF.