Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 308: H894–H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM- Sirt1 −/− ) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (−40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM- Sirt1 −/− mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM- Sirt1 −/− mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout ( C3 −/− ) mice treated with CR was similar to that in the ad libitum-fed C3 −/− mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that cardiac Sirt1 regulates the local complement system during CR.
Oral frailty, first identified in Japan in 2013, refers to a state between healthy oral function and severe decline, marked by minor issues, such as tooth loss and chewing difficulties. The oral frailty five-item checklist (OF-5) enables non-dental professionals to evaluate oral frailty using five key indicators: remaining teeth count, chewing difficulties, swallowing difficulties, dry mouth, and articulatory oral motor skills, and limited studies exist. This study examined the relationship between oral and physical frailties in older adults and assessed the prognosis of physical frailty using the OF-5. Participants aged ≥65 years were recruited from the frail elderly in the Sasayama-Tamba Area study in Sasayama/Tamba area, Hyogo, Japan, and their physical function was assessed in terms of grip strength, walking speed, and skeletal muscle mass. Blood markers, such as cystatin C, an indicator of renal function, were also analyzed. A cross-sectional analysis indicated that oral frailty was correlated with reduced muscle mass, walking speed, and physical function. Women had lower hemoglobin and albumin levels and a greater prevalence of frailty than men. Longitudinal analysis revealed that initial OF-5 scores predicted increased physical frailty after 2–3 years, especially in those with higher baseline scores. The OF-5 was a significant factor for frailty progression in both sexes. These results suggest that early detection of oral frailty via the OF-5 may be useful in preventing the progression of overall frailty in older adults.
Many signaling events induced by ovarian steroid hormones, cytokines, and growth factors are involved in the process of decidualization of human and rodent endometrium. We have reported previously that tyrosine kinase activation of SRC functionally participates in decidualization of human endometrial stromal cells. To address its essential role in decidualization, we examined, using wild-type and Src knockout mice, whether the process of decidualization was impaired in the absence of SRC. Immunohistochemistry using an antibody specific for the active form of SRC revealed that the active SRC was expressed prominently in the decidualizing stromal cells of the pregnant wild-type mouse. Moreover, the active SRC was upregulated in the uterine horn with artificially stimulated decidual reaction. In comparison with wild-type and Src heterozygous mice, the uterus of Src null mice showed no apparent decidual response following artificial stimulation. Ovarian steroid-induced decidualization in vitro, as determined by morphological changes and expression of decidual/trophoblast prolactin-related protein and prostaglandin-endoperoxide synthase 2 (also known as Cox2), both of which are decidualization markers, did not occur in a timely fashion in endometrial stromal cells isolated from the uteri of SRC-deficient mice compared to those from wild-type and Src heterozygous mice. Our results collectively suggest that SRC is an indispensable signaling component for maximal decidualization in mice.
Abstract Background Sarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR). Methods We examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated. Results eGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed ( p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) ( p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia ( p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia ( p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women ( p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men ( p < 0.01). Conclusion In conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.
It remains unclear whether sex differences exist during the development of visceral adipose tissue (VAT) inflammation associated with obesity. The purpose of this study was to clarify sex differences in the occurrence of senescence-related T cells (CD44high PD-1+ CD4+), which play a key role in the progression of VAT inflammation associated with high-fat diet (HFD)-induced obesity. Phase 1: C57BL/6N mice were fed either a control diet (HFC) or HFD for 5 wk. The area under the curve of the oral glucose-tolerance test (oGTT) was maximal at 15 wk in HFD-fed males and at 21 wk in females. At 17 wk, VAT weights were similar, but an increase in the number of macrophages in the VAT was observed only in HFD-fed males. In addition, the numbers of regulatory and senescence-related T cells were consistently higher in males than in females. Phases 2 and 3: 6-wk-old female mice were randomly divided into sham operation and bilateral ovariectomy (OVX) groups and fed either an HFC or HFD from 7 wk. OVX mice were subjected to 17β-estradiol releasing or placebo pellet implantation and fed an HFC. Body and VAT weights were higher in the OVX group than in the sham. The number of macrophages did not change in the OVX group with either diet. HFC-fed OVX mice exhibited high senescence-related T cells in the VAT, resembling HFC-fed male mice. This change was abolished by 17β-estradiol replacement. Thus, we demonstrated different accumulation patterns of VAT immune cells between the sexes, revealing a role for estrogen in the appearance of senescence-related T cells.NEW & NOTEWORTHY The accumulation pattern of adipose tissue differs between the sexes; however, it is unclear whether sex differences exist during the development of adipose tissue inflammation and whether estrogen plays a role. We demonstrated sex differences in immune cells' subpopulation of visceral adipose tissue. The proinflammatory environment appeared earlier in males than in females. In addition, our results suggest that estrogen plays a role in visceral adipose tissue inflammation, particularly by regulating the appearance of senescence-related T cells.
Hypertension is related to impaired mastication that causes malnutrition, declining the general health of older adults. This study assessed the role of dietary intake in the relationship between oral health and blood pressure. Eight hundred ninety-four adults aged ≥65 years who independently lived in rural regions of Japan participated in this study. Hypertension was classified according to the guidelines of the Japanese Society of Hypertension. The oral condition was evaluated by analyzing the remaining teeth, occlusal force, posterior occlusal support, masticatory performance, oral moisture, and oral bacterial level. Dietary intake was assessed using a brief self-administered dietary history questionnaire. Mann-Whitney U, chi-square, Kruskal-Wallis tests, and logistic regression analyses were used to elucidate the factors related to hypertension. Normotensive, hypertensive, and history of hypertension were observed in 30.9%, 23.8%, and 45.3% of the participants, respectively. The factors significantly associated with the hypertension were age, body mass index, posterior occlusal support condition, and sodium-to-potassium ratio related to salt intake and/or vegetable intake. Participants without posterior occlusion significantly had higher risk of hypertension (odds ratio = 1.72). This study suggested that there was an association between oral health and hypertension, while the loss of occlusal support may influence nutritional intake conditions.
