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Although social participation has been reported to be associated with significantly lower risks of mortality and disability, to our knowledge, no study has estimated its impact on disability-free life expectancy (DFLE). Therefore, this study aimed to investigate the association between social participation and DFLE in community-dwelling older people.We analyzed 11-year follow-up data from a cohort study of 11,982 Japanese older adults (age ≥65 years) in 2006. We collected information on the number of social participations using a questionnaire. Using this information, we categorized the participants into four groups. DFLE was defined as the average number of years a person could expect to live without disability. The multistate life table method using a Markov model was employed for calculating DFLE.The results revealed that DFLE according to the number of social participations was 17.8 years (95% confidence interval [CI], 17.3-18.2) for no activities, 20.9 (95% CI, 20.4-21.5) for one activity, 21.5 (95% CI, 20.9-22.0) for two activities, and 22.7 (95% CI, 22.1-23.2) for three activities in men, and 21.8 (95% CI, 21.5-22.2), 25.1 (95% CI, 24.6-25.6), 25.3 (95% CI, 24.7-25.9), and 26.7 years (95% CI, 26.1-27.4), respectively, in women. This difference in DFLE did not change after the participants were stratified for smoking, body mass index, physical activity, and depression.Social participation is associated with longer DFLE among Japanese older people; therefore, encouraging social participation at the population level could increase life-years lived in good health.

AIM Maintaining ≥20 teeth is a public health goal worldwide. Healthy aging, which includes psychological and social well-being, as well as physical indicators, has attracted a great deal of attention with the progression of aging societies. However, no studies have examined the association between the number of remaining teeth and healthy aging. This study aimed to investigate the association between the number of remaining teeth and healthy aging. METHODS This community-based longitudinal cohort study included 8300 Japanese people aged ≥65 years who were free of disability and depression in the baseline survey in 2006. The participants were categorized into four groups according to the number of remaining teeth at baseline: 0-9, 10-19, 20-24 and ≥25. The primary outcome was healthy aging (defined as meeting all four of the following criteria: free of disability, free of depression, high health-related quality of life and high life satisfaction), as assessed by a questionnaire survey carried out in 2017. Multiple logistic regression was used to calculate the corresponding odds ratios and 95% confidence intervals. RESULTS During about 11 years of follow-up, 621 (7.5%) participants attained healthy aging. Participants with ≥20 remaining teeth showed a higher healthy aging rate. Compared with participants with 0-9 teeth, the multivariate-adjusted odds ratios (95% confidence intervals) for 10-19, 20-24 and ≥25 teeth were 0.98 (0.77-1.26), 1.28 (1.01-1.63) and 1.59 (1.24-2.03), respectively. CONCLUSIONS These findings suggest that maintaining ≥20 teeth was associated with healthy aging. Geriatr Gerontol Int 2021; ••: ••-••.

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.

Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63(hi)) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63(-/lo)). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFβ signaling activity through its interaction with TGFβ receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.

Background Our study examined the association between social participation and healthy aging using a community-based cohort study among Japanese older adults. Methods This prospective study was conducted in Ohsaki City, Japan, and included 7226 participants aged ≥65 years at the baseline survey in 2006. We obtained information on frequency of participation in 3 types of community activities (ie, neighborhood activities, hobbies, and volunteer activities) at baseline. Exposure was measured by the number of types of community activities participated in and participants were categorized into 4 groups (ie, none, 1 type, 2 types, and 3 types). The primary outcome was healthy aging as assessed by a questionnaire survey conducted in 2017, and was defined as meeting the following 4 criteria: free of disability, free of depression, high health-related quality of life, and high life satisfaction. We used multiple logistic regression models to calculate the corresponding odds ratios and 95% confidence intervals. Results During 11 years of follow-up, 574 (7.9%) participants attained healthy aging. Compared with participants not participating in any activity, the multivariable-adjusted odds ratios (95% confidence intervals) were 1.90 (1.40, 2.59) for those participating in 1 type, 2.49 (1.84, 3.38) for 2 types, and 3.06 (2.30, 4.07) for 3 types (p for trend < .0001). Furthermore, for each type of community activity, a higher frequency of participation was related to higher probability of healthy aging. Conclusions Our study suggests that social participation is associated with the promotion of healthy aging, and that the benefits were observed across different types of community activities.

Hematopoietic system is one of the main target organs of irradiation injury. Exposure to radiation can cause acute myelosuppression and long-term hematopoietic injury due to the direct and indirect damage of hematopoietic stem cells (HSCs) that can self-renew and differentiate into all types of blood cells. So far, many factors in the modulation of HSC biology at steady status have been revealed, while how to orchestrate HSCs in the context of radiation has not been well established. Recently, an increasing number of studies focus on the underlying mechanisms involved in regulating HSC fate after radiation exposure by affecting DNA damage response (DDR), including DNA-damage repair, cell-cycle arrest, apoptosis and senescence, or bone marrow (BM) microenvironment. In this review, we summarize recent findings on intrinsic and extrinsic factors in the regulation of HSC fate after radiation exposure, which may further deepen our understanding of the radioprotection of HSCs.

To investigate the association of smoking status and years since smoking cessation with the risk of incident dementia among elderly Japanese. We conducted a longitudinal analysis of smoking status and smoking cessation with dementia in prospective cohort study of 12,489 Japanese individuals aged ≥ 65 years who were followed up for 5.7 years. Information on smoking status and other lifestyle factors was collected via a questionnaire in 2006. Data on incident dementia were retrieved from the public Long-term Care Insurance Database. The Cox proportional hazards model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident dementia. During 61,613 person-years of follow-up, 1110 cases (8.9%) of incident dementia were documented. Compared with individuals who had never smoked, current smokers showed a higher risk of dementia (HR 1.46, 95% CI 1.17, 1.80). Among ex-smokers, the risk for those who had stopped smoking for ≤ 2 years was still high (HR 1.39, 95% CI 0.96, 2.01), however, quitting smoking for 3 years or longer mitigated the increased risk incurred by smokers; the multivariable HRs (95% CIs) were 1.03 (0.70, 1.53) for those who had stopped smoking for 3–5 years, 1.04 (0.74, 1.45) for 6–10 years, 1.19 (0.84, 1.69) for 11–15 years, and 0.92 (0.73, 1.15) for > 15 years. Our study suggests that the risk of incident dementia among ex-smokers becomes the same level as that of never smokers if they maintain abstinence from smoking for at least 3 years. Electronic supplementary material The online version of this article (10.1007/s10654-020-00612-9) contains supplementary material, which is available to authorized users.

With population aging, an increasing attention has been paid to quality of life rather than mere longevity. Now, it is urgently needed to clarify predictors of well-being in later life, i.e., "successful aging (SA)." The aim of this study is to investigate whether the number of remaining teeth impacts on maintenance of SA among Japanese older people. The present study was conducted in Tsurugaya district, a suburban area of Sendai, in northern Japan, and included older people aged ≥ 70 years who had met the criteria for SA at a 2003 baseline survey. At the baseline survey, dentists obtained data for the number of remaining teeth. We obtained information about Long-term Care Insurance certification, including the dates of incident functional disability and death between 2003 and 2012. Data pertaining to health-related quality of life (HRQOL) were collected at the 2003 baseline survey and the 2012 follow-up survey. Maintenance of SA was defined in terms of survival, disability-free status and high HRQOL in both 2003 and 2012. Among 450 participants, 108 (24.0%) were considered to have maintained a state of SA. When participants were classified into three groups according to previous studies, in comparison with participants who retained 0-9 teeth, the multivariate prevalence ratios (95% confidence intervals) were 1.39 (0.81-2.36) for those who retained 10-19 teeth and 1.58 (1.002-2.50) for those who retained ≥ 20 teeth (p trend = 0.046). The present results suggest that retaining ≥ 20 teeth is associated with maintenance of SA among Japanese older people.

Rationale: The hematopoietic system and skeletal system have a close relationship, and megakaryocytes (MKs) may be involved in maintaining bone homeostasis. However, the exact role and underlying mechanism of MKs in bone formation during steady-state and stress conditions are still unclear. Methods: We first evaluated the bone phenotype with MKs deficiency in bone marrow by using c-Mpl-deficient mice and MKs-conditionally deleted mice. Then, osteoblasts (OBs) proliferation and differentiation and CD31hiEmcnhi tube formation were assessed. The expression of growth factors related to bone formation in MKs was detected by RNA-sequencing and enzyme-linked immunosorbent assays (ELISAs). Mice with specific depletion of TGF-β1 in MKs were used to further verify the effect of MKs on osteogenesis and angiogenesis. Finally, MKs treatment of irradiation-induced bone injury was tested in a mouse model. Results: We found that MKs deficiency significantly impaired bone formation. Further investigations revealed that MKs could promote OBs proliferation and differentiation, as well as CD31hiEmcnhi vessels formation, by secreting high levels of TGF-β1. Consistent with these findings, mice with specific depletion of TGF-β1 in MKs displayed significantly decreased bone mass and strength. Importantly, treatment with MKs or thrombopoietin (TPO) substantially attenuated radioactive bone injury in mice by directly or indirectly increasing the level of TGF-β1 in bone marrow. MKs-derived TGF-β1 was also involved in suppressing apoptosis and promoting DNA damage repair in OBs after irradiation exposure. Conclusions: Our findings demonstrate that MKs contribute to bone formation through coupling osteogenesis with angiogenesis by secreting TGF-β1, which may offer a potential therapeutic strategy for the treatment of irradiation-induced osteoporosis.

Purpose The association between dairy intake and mortality remains uncertain, and evidence for the Japanese population is scarce. We aimed to investigate the association between dairy intake and all-cause, cancer, and cardiovascular disease (CVD) mortality in Japanese adults. Methods A total of 34,161 participants (16,565 men and 17,596 women) aged 40–64 years without a history of cancer, myocardial infarction, or stroke at baseline were included in the analysis, using data from the Miyagi Cohort Study initiated in 1990. Milk, yogurt, and cheese intake were obtained using a validated food frequency questionnaire. Total dairy intake was calculated as the sum of milk, yogurt, and cheese intake and then categorized by quartile. The outcomes were all-cause, cancer, and CVD mortality. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality risks. Results During 750,016 person-years of follow-up, the total number of deaths was 6498, including 2552 deaths due to cancer and 1693 deaths due to CVD. There was no association between total dairy intake and all-cause, cancer, and CVD mortality for both men and women. We also examined the associations between subgroup dairy products and mortality. For milk and yogurt intake, our results suggest null associations. However, cheese intake was modestly associated with lower all-cause mortality in women; compared with non-consumers, the multivariable HRs (95%CIs) were 0.89 (0.81–0.98) for 1–2 times/month, 0.88 (0.78–1.00) for 1–2 times/week, and 0.89 (0.74–1.07) for 3 times/week or almost daily (p trend = 0.016). Conclusion Dairy intake was not associated with mortality in Japanese adults, except for limited evidence showing a modest association between cheese intake and a lower all-cause mortality risk in women.

Background Both weight loss and cognitive impairment are common in late-life, but it remains unknown whether weight change is associated with risk of incident dementia among elderly Japanese. Our study aimed to investigate the association between long-term weight change since midlife and risk of incident disabling dementia using a community-based cohort study of elderly Japanese. Methods In 2006, we conducted a cohort study of 6,672 disability-free Japanese adults aged ≥65 years. In both 1994 and 2006, the participants reported their weight using a self-reported questionnaire. Based on weight obtained at these two time points, participants were classified into: stable weight (-1.4 - +1.4kg), weight gain (≥ +1.5kg), and weight loss of -2.4 - -1.5kg, -3.4 - -2.5 kg, -4.4 - -3.5kg, -5.4 - -4.5kg, and ≤-5.5kg. Incident disabling dementia was retrieved from the public Long-term Care Insurance database. Participants were followed-up for 5.7 years (between April 2007 and November 2012). Cox proportional hazards model was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident disabling dementia. Results During 32,865 person-years of follow-up, 564 participants were ascertained as having incident disabling dementia. Compared with stable weight, the multivariable-adjusted HRs (95%CIs) were 0.97 (0.70, 1.34) for weight loss of -2.4 - -1.5kg, 0.98 (0.70, 1.38) for -3.4 - -2.5kg, 1.28 (0.91, 1.81) for -4.4 - -3.5kg,1.27 (0.92, 1.77) for -5.4 - -4.5kg, and 1.64 (1.29, 2.09) for ≤-5.5kg. Conclusion Our study suggested that a ≤-3.5kg weight loss over 12 years might be associated with higher risk of incident disabling dementia among elderly Japanese.

Summary Background & aims Previous studies have reported that the Japanese diet is associated with a lower risk of dementia; however, whether changes in adherence to the Japanese diet affects incident dementia remains unknown. We aimed to evaluate the association between long-term changes in adherence to the Japanese diet and risk of incident dementia among older Japanese individuals. Methods We collected dietary information from community-dwelling older individuals living in Ohsaki city, Japan using a validated 39-item food frequency questionnaire in 1994 and 2006. Adherence to the Japanese diet was assessed using the 8-item Japanese Diet Index (JDI8) score (range: 0 to 8 points). Changes in adherence to the Japanese diet were defined as changes in the JDI8 score from 1994 to 2006. Next, the participants were classified into five groups: great decrease, moderate decrease, no changes [ref.], moderate increase, or great increase. Then, 3146 Japanese adults aged ≥65 years in 2006 were followed-up for 5.7 years. Incident dementia was retrieved from the long-term care insurance database. The Cox proportional hazards model was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident dementia. Results During 14,336 person-years of follow up, 231 cases of dementia were ascertained. Compared with no changes in the JDI8 score, the multivariable-adjusted HRs (95%CIs) were 1.72 (1.13, 2.62) for great decrease, 1.10 (0.73, 1.66) for moderate decrease, 0.82 (0.54, 1.25) for moderate increase, and 0.62 (0.38, 1.02) for great increase (p-trend Conclusions An increase in adherence to the Japanese diet was associated with a reduced risk of incident dementia, whereas a decrease in adherence was associated with an elevated risk among older Japanese individuals.

Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34+ and CD41+ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation-induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3-kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1-orchestrated activation of ERK1/2 and Akt signaling.

Long-term hematopoietic output is dependent on hematopoietic stem cell (HSC) homeostasis which is maintained by a complex molecular network in which microRNA play crucial roles, although the underlying molecular basis has not been fully elucidated. Here we show that microRNA-21 (miR-21) is enriched in murine HSC, and that mice with conditional knockout of miR-21 exhibit an obvious perturbation in hematopoiesis. Moreover, significant loss of HSC quiescence and long-term reconstituting ability are observed in the absence of miR-21. Further studies revealed that miR-21 deficiency markedly decreases the nuclear factor kappa B (NF-B) pathway, accompanied by increased expression of PDCD4, a direct target of miR-21, in HSC. Interestingly, overexpression of PDCD4 in wild-type HSC generates similar phenotypes as those of miR-21-deficient HSC. More importantly, knockdown of PDCD4 can significantly rescue the attenuation of NF-B activity, thereby improving the defects in miR-21-null HSC. On the other hand, we found that miR-21 is capable of preventing HSC from ionizing radiation- induced DNA damage via activation of the NF-B pathway. Collectively, our data demonstrate that miR-21 is involved in maintaining HSC homeostasis and function, at least in part, by regulating the PDCD4-mediated NF-B pathway and provide a new insight into radioprotection of HSC.

IntroductionPhysical activity is one of the major modifiable factors for promotion of public health. Although it has been reported that financial incentives would be effective for promoting health behaviours such as smoking cessation or attendance for cancer screening, few randomised controlled trials (RCTs) have examined the effect of financial incentives for increasing the number of daily steps among individuals in a community setting. The aim of this study is to investigate the effects of financial incentives for increasing the number of daily steps among community-dwelling adults in Japan.Methods and analysisThis study will be a two-arm, parallel-group RCT. We will recruit community-dwelling adults who are physically inactive in a suburban area (Nakayama) of Sendai city, Japan, using leaflets and posters. Participants that meet the inclusion criteria will be randomly allocated to an intervention group or a waitlist control group. The intervention group will be offered a financial incentive (a chance to get shopping points) if participants increase their daily steps from their baseline. The primary outcome will be the average increase in the number of daily steps (at 4–6 weeks and 7–9 weeks) relative to the average number of daily steps at the baseline (1–3 weeks). For the sample size calculation, we assumed that the difference of primary outcome would be 1302 steps.Ethics and disseminationThis study has been ethically approved by the research ethics committee of Tohoku University Graduate School of Medicine, Japan (No. 2018-1-171). The results will be submitted and published in a peer-reviewed scientific journal.Trial registration numberUMIN000033276; Pre-results.

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

ObjectiveThe aim of this study was to investigate the effect of a financial incentive on the number of daily walking steps among community-dwelling adults in Japan.Study designTwo-arm, parallel-group randomised controlled trial.Setting/participantsWe recruited physically inactive community-dwelling adults from Sendai city, Japan. Eligible participants were randomly allocated to an intervention or a wait list control group. Pedometers were used to assess the mean number of daily steps in three periods: baseline (weeks 1–3), intervention (weeks 4–6) and follow-up (weeks 7–9).InterventionThe intervention group was offered a financial incentive (shopping points) to meet the target number of increased daily steps in the intervention period.Main outcome measuresThe primary outcome was an increase in the mean number of daily steps in the intervention and follow-up periods compared with baseline.ResultsSeventy-two participants (69.4% women; mean age, 61.2±16.2 years; mean number of daily steps at baseline, 6364±2804) were randomised to the intervention (n=36) and control groups (n=36). During the intervention period, the increase in mean daily steps was significantly higher in the intervention group (1650, 95% CI=1182 to 2119) than in the control group (514, 95% CI=136 to 891; pConclusionsThe present results suggest that financial incentives are effective in promoting short-term increases in physical activity.Trial registration numberUMIN000033276.