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Background With global super-aging, understanding the longitudinal changes in activities of daily living (ADLs) among older adults is critical for maintaining their functional independence, particularly in later life. However, evidence of longitudinal ADL patterns in Asian octogenarians remains limited. This study examined 6-year ADL transition patterns among community-dwelling older adults in Japan aged 85 years or above using latent transition analysis (LTA) to identify dynamic changes and associated factors. Methods The present study used data from the Tokyo Oldest Old Survey on Total Health study, a prospective cohort of 538 participants aged 85 years or older. ADL was assessed using the Barthel index at baseline, 3 years, and 6 years. Through LTA, latent clusters at each time point were identified, and transition probabilities across clusters were estimated. Cluster characteristics and transitions were examined relative to demographic, physical, cognitive, lifestyle, and biological factors. Random forest analysis was used to identify predictors of longitudinal ADL decline. Results Three ADL clusters were identified: “Robust,” “Partially Impaired,” and “Impaired.” Over six years, transitions to worse functional states or mortality were common, particularly among those in the “Partially Impaired” and “Impaired” clusters. Participants in the “Robust” cluster who maintained functional independence demonstrated better physical and cognitive functions, healthier lifestyles, and optimal nutritional and inflammatory profiles. Random forest analysis revealed “Stairs” and “Dressing” as critical predictors of overall ADL deterioration. Conclusions The results contribute to the understanding of aging-related functional trajectories and offer actionable insights for healthcare planning and intervention development. Trial registration This study was approved by the ethics committees of the Keio University School of Medicine (no. 20070047), and written informed consent was obtained from all participants. The TOOTH study was registered in the University Hospital Medical Information Network Clinical Trial Registry under ID UMIN000001842.

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105–109 years), 288 centenarians (100–104 years), and 531 very old people (85–99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity. Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

A healthy diet and regular physical activity (PA) are delineated as healthy behaviours. Their implementation is associated with better health outcomes and improved quality of life. There is less evidence of a relationship between dietary patterns (DP) and PA, especially in adults aged ≥ 85. Hence, this cross-sectional study investigates the association between DP and PA in people of this age group, using the data from The Kawasaki Aging and Well-Being Project. Brief-type self-administered diet history questionnaire was used to estimate the intake of fifty-eight types of food. After energy adjustment, principal component analysis was performed to identify DP. PA was measured objectively using an accelerometer and subjectively using a questionnaire validated for this age group. Thousand participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1 ‘various foods’, DP2 ‘red meats and coffee’, DP3 ‘bread and processed meats’) were identified. DP1 ‘various foods’ was similar to DP previously named ‘healthy’ or ‘prudent’ and showed a positive association with PA time (PAT) as measured by accelerometer (B, 6·25; 95 % CI 0·13, 12·37) and relatively shorter sedentary behaviour (SB) time. DP2 ‘red meats and coffee’ and DP3 ‘bread and processed meats’ were negatively associated with PAT and positively associated with SB time. This study observed the relationship between diet and PA behaviours in adults aged ≥ 85, with healthier and more food-diverse DP associated with longer PAT and relatively unhealthy DP with shorter PAT.

As the world's population is ageing, improving the physical performance (PP) of the older population is becoming important. Although diets are fundamental to maintaining and improving PP, few studies have addressed the role of these factors in adults aged ≥ 85 years, and none have been conducted in Asia. This study aimed to determine the dietary patterns (DP) and examine their relationship with PP in this population. This cross-sectional study (Kawasaki Aging and Wellbeing Project) estimated food consumption using a brief-type self-administered diet history questionnaire. The results were adjusted for energy after aggregating into thirty-three groups, excluding possible over- or underestimation. Principal component analysis was used to identify DP, and outcomes included hand grip strength (HGS), timed up-and-go test, and usual walking speed. This study was set throughout several hospitals in Kawasaki city. In total, 1026 community-dwelling older adults (85-89 years) were enrolled. Data of 1000 participants (median age: 86·9 years, men: 49·9 %) were included in the analysis. Three major DP (DP1: various foods, DP2: red meats and coffee, DP3: bread and processed meats) were identified. The results of multiple regression analysis showed that the trend of DP2 was negatively associated with HGS (B, 95 % CI -0·35, -0·64, -0·06). This study suggests a negative association between HGS and DP characterised by red meats and coffee in older adults aged ≥ 85 years in Japan.

Mass production of numerous secondary plant and microbial metabolites is crucial, given their value as pharmaceutical agents, dietary supplements, and pesticides. For microbial strain, mass production generally involves improving the native producer strain to enhance overall productivity via spontaneous mutagenesis or genetic modifications. Alternatively, productivity can be enhanced through heterologous production, in which the biosynthetic genes for a secondary metabolite are expressed in a more suitable strain. However, as these biosynthetic genes commonly exist as long clusters, often exceeding several tens of kilobases (kb), their handling is labor-intensive and time-consuming, requiring multiple rounds of genetic cloning and introduction into the host. Therefore, methods enabling efficient transfer of biosynthetic genes into another microorganism in a single step of transformation without the need to clone long gene clusters have been strongly desired. Such an approach has been explored in filamentous fungi, however the maximum gene size sufficiently transferred with the approach thus far is only approximately 20 kb. In this study, we transferred 63 kb pairs of DNA encoding a secondary metabolite-biosynthetic genes into the chromosome of Aspergillus oryzae , a filamentous fungus, using a single-step transformation approach based on multiple homologous recombination events. This study expands the potential of using A. oryzae as a host for efficient heterologous metabolite production. The results serve as a useful reference, providing insights, such as the DNA fragment number and assembled cluster length in host cells, for the cases where heterologous production of a secondary metabolite proves desirable in filamentous fungi. Key points • One-step transfer of 24 DNA fragments to A. oryzae and the in vivo ordered assembly. • The assembled 63 kb DNA region enabled heterologous secondary metabolite production. • The transfer method adopted in this study may be applied to other filamentous fungi.

Background The relationship between inflammatory response, fish consumption, and mortality risk in older individuals is unclear. We investigated whether C-reactive protein (CRP) levels ≥ 0.1 mg/dL, fish intake, and inflammatory responses are associated with all-cause mortality risk in older adults. Methods This prospective cohort study included older adults aged 85–89 years from the Kawasaki Aging and Wellbeing Project, who did not require daily care. Cohort was recruited from March 2017 to December 2018 (follow-up ended on December 31, 2021). Dietary assessment was conducted using the Brief Self-Administered Diet History Questionnaire. Multivariate Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality in the CRP ≥ 0.1 mg/dL group; the CRP < 0.1 mg/dL group was used for reference. Within CRP ≥ 0.1 and < 0.1 mg/dL groups, participants were categorized into tertiles of fish intake. HRs and 95% CIs for all-cause mortality in the other groups were estimated using the lower tertile group as a reference. Results The study included 996 participants (mean [standard deviation] age, 86.5 [1.37] years; 497 [49.9%] women) with a median CRP level of 0.08 (interquartile range [IQR] = 0.04–0.16). There were 162 deaths during 4,161 person-years of observation; the multivariable-adjusted HR for all-cause mortality in the CRP ≥ 0.1 mg/dL group was 1.86 (95% CI, 1.32–2.62); P  < 0.001. In 577 individuals with median (IQR) fish intake of 39.3 g/1000 kcal (23.6–57.6) and CRP level of < 0.1 mg/dL, the multivariable-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 1.15 (0.67–1.97); P  = 0.59, non-linear P  = 0.84. In 419 individuals with median (IQR) fish intake of 40.7 g/1000 kcal (25.0–60.1) and CRP level of ≥ 0.1 mg/dL, the multivariate-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 0.49 (0.26–0.92); P  = 0.026, non-linear P  = 0.38, P-value for interaction = 0.040. Conclusions A negative association between fish intake and all-cause mortality was seen in older adults with elevated CRP levels, which is a mortality risk factor. While the results may be limited owing to stringent methods ensuring impartiality, they offer valuable insights for future research. Trial registration UMIN000026053. Registered February 24, 2017.

Background On April 7, 2020, Japan declared a state of emergency due to the first wave of coronavirus disease 2019 (COVID-19) with the associated social distancing likely to have had a great impact on older adults’ lifestyle and health. This study aimed to explore the behavioral changes and personal hygiene practices in relation with background psychosocial and health characteristics of older adults during the COVID-19 emergency. Methods A cross-sectional telephonic survey was conducted with the participants of the Kawasaki Aging and Wellbeing Project (KAWP), an on-going longitudinal cohort study of older adults aged 85 or older. The interviews were conducted using a structured questionnaire consisting of 11 closed questions regarding behavioral changes and personal hygiene practices during the state of emergency. Sociodemographic and health data were obtained from the KAWP baseline survey conducted 2.2 years before the telephonic survey. Results Overall, 487 participants from the KAWP responded to the telephonic survey (response rate: 89.2%). 94.5% of the respondents reported no changes in basic lifestyle habits, such as eating, sleeping, smoking, and drinking, whereas 28.1% reported a decrease in physical activity, and 54.6% reported going out less frequently. One-third of the respondents reported a decrease in the number of people to converse with, as well as the amount of time to converse. For personal hygiene practices, 93.8% reported wearing a mask when they went out, and 50.3% reported an increased frequency of handwashing. Multiple logistic regression analysis revealed that engagement in physical activity at baseline (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.23–3.08), smartphone ownership (OR = 2.15, 95% CI = 1.33–3.47), and visual impairment (OR = 1.79; 95% CI = 1.10–2.91) were independently associated with decreased physical activity during the COVID-19 emergency. Female respondents and smartphone ownership were significantly associated with more frequent handwashing. Conclusions The study revealed that older adults in an urban setting responded to the COVID-19 emergency with behavioral changes. The findings of this study have implications for the design of preventive strategies to maintain the health and wellbeing of at-risk older adults.

Dietary questionnaires for assessing dietary intakes among populations of individuals aged 80 years or older (the very old) are very limited. We examined the relative validity of forty-three nutrients and twenty-seven food groups estimated by a brief-type self-administered diet history questionnaire (BDHQ) targeting very old Japanese, using semi-weighed dietary records (DR) as a reference. Between June and August 2012 and between June 2015 and February 2016, a three-day non-consecutive DR (at two-week intervals) and a BDHQ were completed. Tokyo, the capital prefecture of Japan. Eighty very old Japanese (thirty-six men and forty-four women) aged 82-94 years. The median intakes of 40-70 % of the crude and energy-adjusted nutrients estimated by the BDHQ were significantly different from those estimated by the DR. The median Spearman's correlation coefficient of nutrient intakes between the BDHQ and the DR was 0·39-0·46. About half (48-56 %) of the food groups were significantly different in terms of the median intakes estimated by the BDHQ and the DR in crude and energy-adjusted values. The median Spearman's correlation coefficient between the BDHQ and the DR was 0·45-0·48. Acceptable Spearman's correlations (≥0·3) were obtained for many dietary intakes among the very old Japanese population. The BDHQ is a good candidate for epidemiological studies among very old Japanese, although, for some nutrients and food groups, the difficulty of estimating accurate median intakes is one of the limitations for the tool. Further efforts to enhance the validity of the BDHQ for very old populations are needed.

ObjectiveThis study aimed to identify associations between multimorbidity and subjective health outcomes among the very old persons, after adjusting for coexisting conditions such as frailty and depression.Study setting and participantsThis was an observational cross-sectional study involving 1012 independent, community-dwelling very old persons (507 men, 505 women; aged 85–89 years) in Kawasaki city, Japan.Outcome measuresThe primary outcome was the cross-sectional associations between multimorbidity and poor self-rated health (SRH) and life satisfaction using binary logistic regression. The secondary outcome was the association of subjective health with each chronic condition.ResultsThe prevalence of multimorbidity (≥2 conditions) was 94.7%, and the average number of chronic conditions was 4.47±1.9. Multimorbidity was significantly associated with poor SRH in the adjusted model only when six or more chronic conditions were present (OR 4.80; 95% CI 1.34 to 17.11; p=0.016). Cerebrovascular disease, heart disease, respiratory disease, connective tissue disease and arthritis showed significant associations with poor SRH after multivariate adjustment. Sex-specific analysis replicated associations between multimorbidity with six or more conditions and SRH in both men and women, while the diseases with the greatest impact on SRH differed between men and women. Most conditions were not associated with low satisfaction with life scale, with the exception of arthritis (OR 1.92, 95% CI 1.32 to 2.78, p=0.001).ConclusionsMultimorbidity is prevalent in the independent, community-dwelling very old persons and is associated with poor SRH when six or more conditions are present; conditions causing mobility limitations, such as cerebrovascular disease, connective tissue disease and arthritis, have a negative impact on SRH.Trial registration numberUMIN000026053.

Background Associations between physical activity (PA) and quality of life (QOL) have usually been studied in people in their 60s and 70s, however little is known about these associations in older age groups. We aimed to examine the association between PA and QOL in Japanese adults aged 85–89 years and investigate the types of exercises/sports in this population. Methods This cross-sectional study ( n  = 914) used baseline data from the Kawasaki Aging and Well-being Project (KAWP), a longitudinal cohort study of older adults aged 85–89 years. Health-related QOL and psychological well-being were assessed using the EuroQoL 5D-5L (EQ-5D-5L) and the WHO Five Well-Being Index (WHO-5), respectively. PA was objectively and subjectively measured using a triaxial accelerometer and modified Zutphen Physical Activity Questionnaire, respectively. Associations were analyzed using multivariable regression analysis. Results Higher PA was significantly associated with a higher EQ-5D-5L index score (coefficient, 0.004; 95%CI [0.001, 0.008], standardized coefficient, 0.142). In contrast, no association was observed between PA and the WHO-5 total score (coefficient, 0.103; 95%CI [-0.066, 0.271], standardized coefficient, 0.068). Calisthenics were the most commonly performed sports or exercises (27.4% of male and 47.6% of female participants). The subgroup of participants with > median PA had a longer walking duration than their counterparts, and the following sports/exercises were more frequently performed in addition to calisthenics; resistance training and others among male participants: stretching/yoga among female participants. Conclusions Our findings suggest that PA is associated with a better health-related QOL. However, no association was observed between PA and psychological well-being in this population. We found that calisthenics were the most commonly performed and that more physically active older adults performed several types of exercises/sports in addition to calisthenics and walking for longer durations. Since few studies have investigated the types of exercises/sports in this age group, these findings would be helpful for interventions to maintain PA and QOL in this age group. Trial registration UMIN000026053.