Estrogen contributes to the sex difference in the occurrence of senescence-related T cells during the development of visceral adipose tissue inflammation.

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 17ß-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 17ß-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.

Decline of instrumental activities of daily living is a risk factor for nutritional deterioration in older adults: a prospective cohort study.

BACKGROUND: The association between functional capacity and the subsequent risk of nutritional deterioration is yet to be understood. The purpose of this study was to elucidate the relationship between functional capacity, comprising instrumental activities of daily living (IADL), intellectual activity, and social function, and future decline in nutritional status. METHODS: The current study is a two-year prospective cohort study. A total of 468 community-dwelling older adults without nutritional risks were enrolled. We used the Mini Nutritional Assessment Screening Form. Functional capacity, including IADL, intellectual activity, and social function, was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline. The nutritional status was reassessed at a 2-year follow-up. Risk ratios (RR) of functional capacity for the incidence of nutritional decline were estimated. RESULTS: Low functional capacity was significantly associated with future deterioration of nutritional status (RR 1.12, 95% confidence interval [CI] 1.02-1.25). Of the subdomains of functional capacity, IADL decline (adjusted RR 2.21, 95% CI 1.18-4.13) was an independent risk factor for the incidence of nutritional risk. Intellectual and social activities were not significant. CONCLUSION: Decline in functional capacity, especially IADL, is a risk factor for future deterioration in nutritional status. Further studies are required to elucidate the effect of interventions for IADL decline on maintaining nutritional status in older adults.

[Association between physical activity and apathy among community-dwelling older adults].

AIM: To determine the association between physical activity and apathy in community-dwelling older adults. METHODS: This was a cross-sectional study. Apathy was assessed using three sub-items from the Geriatric Depression Scale 15 (GDS-3A) on apathy syndrome. Physical activity was measured using a wrist-worn accelerometer. Exercise intensity was classified as sedentary behavior, light-intensity physical activity, or moderate-to-vigorous-intensity physical activity. A logistic regression analysis was used to examine the association between apathy and physical activity for each exercise intensity level. RESULTS: Seven-hundred and eighty-four participants (age 72.7±5.9 years old) were included. Of those, 103 (13.1%) were in the apathy group. A multivariate analysis adjusted for demographic factors revealed that decreased total physical activity (odds ratio [OR] = 0.947, 95% confidence interval [CI] = 0.912-0.984, p = 0.005), light-intensity physical activity (OR = 0.941, 95% CI = 0.899-0.985, p = 0.009), and increased sedentary behavior (OR = 1.002, 95% CI = 1.001-1.003, p = 0.007) were associated with a greater OR of apathy, although moderate-to-vigorous-intensity physical activity was not significant (OR = 0.916, 95% CI = 1.826-1.017, p = 0.100). However, in the final model adjusted for depressive symptoms and functional factors, the association was not found to be significant, and a strong association was observed between depressive symptoms and apathy. CONCLUSION: Physical activity in older adults with apathy symptoms was decreased in this study. However, the associations seemed to be strongly affected by depressive symptoms, and physical activity was not independently associated with apathy.

Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia.

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.

Physical frailty predicts the development of social frailty: a prospective cohort study.

BACKGROUND: It has not been clarified whether physical frailty symptoms predict social. frailty. The purpose of this study was to elucidate the effect of physical frailty on social frailty, and to determine which domains of physical frailty predict the development of social frailty. METHODS: We employed a two-year prospective cohort study. A total of 342 socially robust community-dwelling older adults were recruited. We used a modified social frailty screening index consisting of four social domains including financial difficulties, living alone, social activity, and contact with neighbors. Physical frailty status was also assessed at baseline. At the two-year follow-up, we assessed the development of social frailty. Social status was assessed using four social subdomains for the primary analysis. Social status was assessed using the two social subdomains of social activity and contact with neighbors, which would be affected by the physical frailty component, for the secondary analysis. The risk ratios (RR) of physical frailty for the development of social frailty were estimated. RESULTS: Although physical frailty symptoms were not a significant risk factor for future development of social frailty as assessed by four social subdomains (adjusted RR 1.39, 95% CI 0.95-2.15), it became significant when development of social frailty was assessed by the two social subdomains (adjusted RR 1.78, 95% CI 1.10-2.88). An analysis using the physical frailty subdomain showed that slow gait speed (adjusted RR 3.41, 95% CI 1.10-10.53) and weakness (adjusted RR 1.06, 95% CI 1.01-1.12) were independent risk factors for development of social frailty as assessed by two social subdomains. CONCLUSIONS: Physical frailty symptoms predict the development of social frailty. Among physical frailty subdomains, gait speed and muscle strength are critical independent risk factors for future decline in the social aspect. The prevention of physical frailty, especially by maintaining gait ability and muscle strength, may be effective for avoiding social frailty.

Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

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.

Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.

Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion injury (IRI). We previously found that treatment with N(G)-nitro-l-arginine methyl ester completely abrogates CR-induced cardioprotection and increases nuclear sirtuin 1 (Sirt1) expression. However, it remains unclear whether endothelial nitric oxide (NO) synthase (eNOS) plays a role in CR-induced cardioprotection and Sirt1 activation. We subjected eNOS-deficient (eNOS(-/-)) mice to either 3-mo ad libitum (AL) feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia followed by 60-min reperfusion. The degree of myocardial IRI in AL-fed eNOS(-/-) mice was more severe than that in AL-fed wild-type mice. Furthermore, CR did not exert cardioprotection in eNOS(-/-) mice. eNOS(-/-) mice exhibited elevated blood pressure and left ventricular hypertrophy compared with wild-type mice, although they underwent CR. Although nuclear Sir1 content was increased, the increases in cardiac Sirt1 activity with CR was absent in eNOS(-/-) mice. In eNOS(-/-) mice treated with hydralazine, blood pressure and left ventricular weight became comparable with CR-treated wild-type mice. However, CR-induced cardioprotection was not observed. Resveratrol enhanced cardiac Sirt1 activity but failed to mimic CR-induced cardioprotection in eNOS(-/-) mice. Finally, combination therapy with resveratrol and hydralazine attenuated myocardial IRI and reduced infarct size in eNOS(-/-) mice, and their effects were comparable with those observed in CR-treated wild-type mice. These results demonstrate the essential roles of eNOS in the development of CR-induced cardioprotection and Sirt1 activation during CR. The combination of a relatively low dose of resveratrol with an adequate vasodilator therapy might be useful for managing patients with endothelial dysfunction associated with impaired NO bioavailability.

Do the physical activity questions in the Japanese version of the Cardiovascular Health Study criteria truly reflect a decline in physical activity?

Older participants identified as having decreased physical activity according to the Japanese version of the Cardiovascular Health Study criteria did not show a significant reduction in accelerometer-measured physical activity. Despite its widespread use in Japanese studies, the Japanese version of the Cardiovascular Health Study physical activity questionnaire may not effectively capture declines in physical activity.

Factors contributing to subjective well-being and supporting successful aging among rural Japanese community-dwelling older adults: A cross-sectional and longitudinal study.

AIM: We aimed to identify the factors contributing to subjective well-being in community-dwelling older adults in rural Japan. This study explored the relationship among physical and mental health, socioeconomic status, and activity levels with regard to the subjective well-being of older adults. METHODS: In the Frail Elderly in the Sasayama-Tamba Area study, a cohort investigation of independent older adults in a rural Japanese community, 541 of 844 participants completed a 2-year follow-up survey. Subjective well-being was assessed as a binary based on three factors - "happiness," "satisfaction with life" and "meaning in life" - using a subset of the World Health Organization's Quality of Life questionnaire. The improvement group transitioned from not having subjective well-being during the baseline survey to having subjective well-being during the follow-up survey. Furthermore, we used multivariable log-Poisson regression models to calculate the prevalence ratios of subjective well-being. RESULTS: The cross-sectional study showed that sleep satisfaction, health services access satisfaction and having a higher-level functional capacity were positively associated with having "happiness" and "satisfaction with life." Furthermore, being aged ≥ 80 years and having financial leeway were positively associated with having "meaning in life." The longitudinal study showed that having a higher-level functional capacity was positively associated with improving "happiness" and "satisfaction with life." Being female was positively associated with improving "happiness" and "meaning in life," and health services access satisfaction and alcohol drinking were positively associated with improving "satisfaction with life" and "meaning in life," respectively. CONCLUSIONS: These findings offer promising avenues for enhancing the subjective well-being of older adults. Geriatr Gerontol Int 2024; 24: 311-319.

Association between Bone Quality and Physical Activity in Community-Dwelling Older Adults.

Bone quality is an essential factor determining bone strength. However, the relationship between physical activity (PA) and bone quality remains unclear. This study aimed to ascertain the relationship between bone quality and PA using a cortical bone quantitative ultrasound device that measures components of bone quality. In this cross-sectional study, bone quality was assessed in community-dwelling older adults by measuring the cortical speed of sound (cSOS) at the mid-tibia using a quantitative ultrasound device. Using a wrist-worn accelerometer, we calculated the daily duration of moderate-to-vigorous physical activity (MVPA) and light physical activity (LPA) based on estimated METs from the accelerometer data, without differentiating between types of activities. A multiple regression analysis was performed to examine the association between PA and the cSOS. The participants' physical activity averaged 42.0 min/day for MVPA and 483.6 min/day for LPA. No significant association was observed between PA and bone quality in either men or women in the crude models. Furthermore, PA was not significantly correlated with the cSOS in the models adjusted for age, body mass index, nutrient intake, number of medications, and kidney disease. This study was a cross-sectional study which focused on the association between bone quality in older adults and their current amount of PA. The cSOS, as a measure of bone quality, was not associated with PA in men or women. Higher amounts of daily PA, as estimated from metabolic equivalents with an accelerometer, may not necessarily maintain or improve bone quality in older adults. This study does not rule out the potential for a positive association between PA levels or types and bone quality in younger or middle-aged individuals. It was specifically targeted at older adults, and its findings should not be generalized to younger populations. Further longitudinal studies are required to better understand the relationship between PA and bone quality.

Caloric restriction primes mitochondria for ischemic stress by deacetylating specific mitochondrial proteins of the electron transport chain.

RATIONALE: Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion. OBJECTIVE: The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection. METHODS AND RESULTS: Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H(2)O(2) production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske subunit in the CR heart. Low-dose resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose resveratrol. CONCLUSIONS: These results strongly suggest that CR primes mitochondria for stress resistance by deacetylating specific mitochondrial proteins of the electron transport chain. Targeted deacetylation of NDUFS1 and/or Rieske subunit might have potential as a novel therapeutic approach for cardioprotection against ischemia/reperfusion.

Association Between Timed Up-and-Go Test and Future Changes in the Frailty Status in a Longitudinal Study of Japanese Community-Dwelling Older Adults.

Purpose: This study aimed to evaluate the relationship between timed up-and-go (TUG) test time and changes in frailty status in a longitudinal cohort study of rural Japanese older adults. Patients and Methods: This prospective cohort study included 545 community-dwelling older adults. Initial and 2-year follow-up surveys were conducted. We compared the number of the Japanese version of the Cardiovascular Health Study components during the follow-up period and classified the participants into three groups: the favorable change, unchanged as prefrail, and unfavorable change groups. Associations between changes in frailty status and TUG time in the first survey were examined. The predictive ability of the TUG test was determined using the receiver operating characteristic (ROC) curve. Results: The favorable change group comprised 315 individuals (57.8%), the unchanged as prefrail group 105 (19.2%), and the unfavorable change group 125 (22.9%). TUG time was associated with the favorable and unfavorable changes after adjustment for covariates (OR 0.79, 95% CI 0.68-0.92, P=0.001 and OR 1.27, 95% CI 1.09-1.49, P=0.002). The ROC curve of TUG time as a predictor of unfavorable changes showed an area under the curve of 0.59. A cut-off point of TUG was calculated as 6.3 s with 49.6% sensitivity and 66.0% specificity. Conclusion: TUG time in the first survey was significantly associated with changes in frailty status 2 years later. However, its predictive value as a stand-alone test is limited and has the potential to predict future changes in the frailty status in older adults in combination with other tests.

Impact of quality of life on future frailty status of rural Japanese community-dwelling older adults.

OBJECTIVES: We aimed to clarify the factors that contribute to the improvement or progression of frailty in rural Japanese community-dwelling older adults. METHODS: Of the 840 participants in the cohort study of independent older adults aged 65 years and older living in the Tamba-Sasayama area of Hyogo Prefecture (FESTA study) from September 2016 to December 2017, 551 participated in the 2-year follow-up survey from September 2018 to December 2019. METHODS: We evaluated clinical background, physical and cognitive function, total physical activity, daily protein intake, quality of life (QOL) using the WHOQOL-BREF (WHOQOL-26), and frailty status diagnosed using the Japanese version of the Cardiovascular Health Study. We compared the frailty status at the initial and follow-up examinations and classified the participants into three groups: improvement, unchanged, and worsening. Each parameter was compared among the three groups and the factors contributing to the improvement or worsening of frailty status were analyzed using a modified Poisson regression analysis. RESULTS: The median age at the first survey was 72 years (range: 68-76); 190 men and 361 women were enrolled. The improvement group consisted of individuals with a change in status from frail to prefrail/robust and from prefrail to robust (n = 114); the worsening group consisted of individuals with a change in status from robust to prefrail/frail and from prefrail to frail (n = 92). The physical domain of QOL was significantly associated with an improvement in frailty status independent of the frailty status at baseline. Contrastingly, any domains of QOL were not significantly associated with a worsening frailty status. CONCLUSIONS: This study demonstrated for the first time that QOL has a significant impact on the future improvement and progression of frailty status and that QOL conditions and frailty status affect older adults bidirectionally.

Relationships between cystatin C and creatinine-based eGFR with low tongue pressure in Japanese rural community-dwelling older adults.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD), which is defined as a low estimated glomerular filtration rate (eGFR). It has been reported that oral hypofunction characterized by decreased tongue pressure is related to sarcopenia. Although there are several previous reports regarding the association of renal dysfunction with oral hypofunction characterized by low tongue pressure, the association between tongue pressure and renal function is not fully understood. METHODS: This cross-sectional study included 68 men aged 79.0 ± 4.8 years and 145 women aged 77.3 ± 5.4 years from a rural area in Hyogo Prefecture, Japan. We examined the relationships between cystatin C-based CKD (CKDcys), creatinine-based CKD (CKDcre), ratio of cystatin C-based GFR (eGFRcys) divided by creatinine-based GFR (eGFRcre): eGFRcys/eGFRcre, and tongue pressure in community-dwelling older adults. RESULTS: Tongue pressure was significantly lower in participants with CKDcys than in those without CKDcys in men and women. However, there were no significant differences in tongue pressure with or without CKDcre. Tongue pressure was significantly lower in participants with eGFRcys/eGFRcre <1.0, than in those with eGFRcys/eGFRcre ≧ 1.0 in men. According to the receiver operating characteristic analysis, the optimal cut-off value of tongue pressure for the presence of CKDcys was 36.6kPa, area under the curve (AUC) 0.74 (specificity 54.8%, sensitivity 84.6%) in men and 31.8kPa, AUC 0.65 (specificity 67.3%, sensitivity 60.5%) in women. CONCLUSIONS: CKDcys but not CKDcre is associated with low tongue pressure. In addition, a lower eGFRcys/eGFRcre ratio is a useful screening marker of low tongue pressure in community-dwelling older adults.

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

OBJECTIVES: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. DESIGN: The current study was a retrospective cross-sectional study. SETTING AND PARTICIPANTS: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. MEASURES: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. CONCLUSIONS AND IMPLICATIONS: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

The Association of Dietary Intake, Oral Health, and Blood Pressure in Older Adults: A Cross-Sectional Observational Study.

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.

Impact of long-term caloric restriction on cardiac senescence: caloric restriction ameliorates cardiac diastolic dysfunction associated with aging.

Approximately half of older patients with congestive heart failure have normal left ventricular (LV) systolic but abnormal LV diastolic function. In mammalian hearts, aging is associated with LV diastolic dysfunction. Caloric restriction (CR) is expected to retard cellular senescence and to attenuate the physiological decline in organ function. Therefore, the aim of the present study was to investigate the impact of long-term CR on cardiac senescence, in particular the effect of CR on LV diastolic dysfunction associated with aging. Male 8-month-old Fischer344 rats were divided into ad libitum fed and CR (40% energy reduction) groups. LV function was evaluated by echocardiography and cardiac senescence was compared between the two groups at the age of 30-month-old. (1) Echocardiography showed similar LV systolic function, but better LV diastolic function in the CR group. (2) Histological analysis revealed that CR attenuated the accumulation of senescence-associated ß-galactosidase and lipofuscin and reduced myocyte apoptosis. (3) In measurements of [Ca(2+)](i) transients, the time to 50% relaxation was significantly smaller in the CR group, whereas F/F(0) was similar. (4) CR attenuated the decrease in sarcoplasmic reticulum calcium ATPase 2 protein with aging. (5) CR suppressed the mammalian target of rapamycin (mTOR) pathway and increased the ratio of conjugated to cytosolic light chain 3, suggesting that autophagy is enhanced in the CR hearts. In conclusion, CR improves diastolic function in the senescent myocardium by amelioration of the age-associated deterioration in intracellular Ca(2+) handling. Enhanced autophagy via the suppression of mTOR during CR may retard cardiac senescence.

The UDP-glucose receptor P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8.

Innate mucosal immune responses, including recognition of pathogen-associated molecular patterns through Toll-like receptors, play an important role in preventing infection in the female reproductive tract (FRT). Damaged cells release nucleotides, including ATP and uridine 5'-diphosphoglucose (UDP-glucose), during inflammation and mechanical stress. We show in this report that P2RY14, a membrane receptor for UDP-glucose, is exclusively expressed in the epithelium, but not the stroma, of the FRT in humans and mice. P2RY14 and several proinflammatory cytokines, such as IL-8, are up-regulated in the endometria of patients with pelvic inflammatory disease. UDP-glucose stimulated IL-8 production via P2RY14 in human endometrial epithelial cells but not stromal cells. Furthermore, UDP-glucose enhanced neutrophil chemotaxis in the presence of a human endometrial epithelial cell line in an IL-8-dependent manner. Administration of UDP-glucose into the mouse uterus induced expression of macrophage inflammatory protein-2 and keratinocyte-derived cytokine, two murine chemokines that are functional homologues of IL-8, and augmented endometrial neutrophil recruitment. Reduced expression of P2RY14 by small interfering RNA gene silencing attenuated LPS- or UDP-glucose-induced leukocytosis in the mouse uterus. These results suggest that UDP-glucose and its receptor P2RY14 are key front line players able to trigger innate mucosal immune responses in the FRT bypassing the recognition of pathogen-associated molecular patterns. Our findings would significantly impact the strategic design of therapies to modulate mucosal immunity by targeting P2RY14.

The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice.

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered "senescence-associated T cells" in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.

Association between Physical Frailty Subdomains and Oral Frailty in Community-Dwelling Older Adults.

This cross-sectional study aimed to demonstrate the association between physical frailty subdomains and oral frailty. This study involved community-dwelling older adults (aged ≥65 years). Physical frailty was assessed with the Japanese version of the Cardiovascular Health Study criteria. Oral frailty was defined as limitations in at least three of six domains. Logistic regression analysis was used to analyze the association between physical frailty risk and oral frailty. In addition, we examined the association between physical frailty subdomains (gait speed, grip strength, exhaustion, low physical activity, and weight loss) and oral frailty. A total of 380 participants were recruited for this study. Overall, 18% and 14% of the participants were at risk of physical frailty and had oral frailty, respectively. Physical frailty risk (odds ratio (OR) = 2.40, 95% confidence interval (CI): 1.22-4.75, p = 0.012) was associated with oral frailty in multivariate analysis. In secondary analysis, among physical frailty subdomains, gait speed (OR = 0.85, 95% CI: 0.73-0.97, p = 0.019) was associated with oral frailty. The present findings suggest that physical frailty is closely related to oral frailty. Among physical frailty subdomains, decreased gait speed in particular is an important indicator related to the development of oral frailty.