Explore the vast range of titles available.

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.

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases 1 – 3 . Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium . These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis. The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive—but not Gram-negative—multidrug-resistant pathogens.

Engagement in leisure activities has been claimed to be highly beneficial in the elderly. Practicing such activities is supposed to help older adults to preserve cognitive function, physical function, and mental health, and thus to contribute to successful aging. We used structural equation modeling (SEM) to analyze the impact of leisure activities on these constructs in a large sample of Japanese older adults (N = 809; age range 72-74). The model exhibited an excellent fit (CFI = 1); engaging in leisure activities was positively associated with all the three successful aging indicators. These findings corroborate previous research carried out in Western countries and extend its validity to the population of Eastern older adults. Albeit correlational in nature, these results suggest that active engagement in leisure activities can help older adults to maintain cognitive, physical, and mental health. Future research will clarify whether there is a causal relationship between engagement in leisure activities and successful aging.

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.

To assess the relationship between polydoctoring and patient outcomes, we conducted a retrospective cohort study using a Japanese population-based dataset from April 2014 to December 2022. Overall, 2,338,965 patients aged 75–89 years with at least two chronic conditions were included. Polydoctoring was assessed by the number of regularly visited facilities (RVFs). The primary outcome was all-cause mortality, with secondary outcomes being all-cause hospitalizations, hospitalizations for ambulatory care-sensitive conditions (ACSCs), and outpatient costs. During the study period, 14.5% of participants died, 52.2% were hospitalized, and 12.5% experienced ACSC-related hospitalizations. Patients without RVFs had the highest mortality risk (HR: 3.23, 95% CI: 3.14–3.33), while those with ≥ 5 RVFs had the lowest (HR: 0.67, 95% CI: 0.62–0.73). ACSC-related hospitalizations were U-shaped, with increased risk at ≥ 5 RVFs (HR: 1.13, 95% CI: 1.06–1.22). Outpatient costs increased 3.21 times for ≥ 5 RVFs compared to 1 RVF. Polydoctoring was associated with reduced mortality but higher hospitalization rates and costs, with an optimal RVF range of 2–3 which minimized ACSC-related admissions. These findings emphasize the need for strategies that balance the benefits and costs of polydoctoring to support sustainable healthcare through improved care coordination and resource management for aging populations.

Superoxide dismutase 3 ( SOD3 ), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.

Understanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth whole-genome sequence (WGS) data (25.9×). Using rare singletons, we identify signals of very recent selection for the past 2000–3000 years in multiple loci (ADH cluster, MHC region, BRAP-ALDH2 , SERHL2 ). In large-scale genome-wide association study (GWAS) dataset ( n  = 171,176), variants with selection signatures show enrichment in heterogeneity of derived allele frequency spectra among the geographic regions of Japan, highlighted by two major regional clusters (Hondo and Ryukyu). While the selection signatures do not show enrichment in archaic hominin-derived genome sequences, they overlap with the SNPs associated with the modern human traits. The strongest overlaps are observed for the alcohol or nutrition metabolism-related traits. Our study illustrates the value of high-depth WGS to understand evolution and their relationship with disease risk. Recent natural selection left signals in human genomes. Here, Okada et al. generate high-depth whole-genome sequence (WGS) data (25.9×) from 2,234 Japanese people of the BioBank Japan Project (BBJ), and identify signals of recent natural selection which overlap variants associated with human traits.

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.

High levels of circulating adiponectin are associated with increased insulin sensitivity, low prevalence of diabetes, and low body mass index (BMI); however, high levels of circulating adiponectin are also associated with increased mortality in the 60-70 age group. In this study, we aimed to clarify factors associated with circulating high-molecular-weight (cHMW) adiponectin levels and their association with mortality in the very old (85-89 years of age) and centenarians. The study included 812 (women: 84.4%) for centenarians and 1498 (women: 51.7%) for the very old. The genomic DNA sequence data were obtained by whole-genome sequencing or DNA microarray-imputation methods. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate regression analyses were used to evaluate cHMW adiponectin characteristics and associated factors. All-cause mortality was analyzed in three quantile groups of cHMW adiponectin levels using Cox regression. The cHMW adiponectin levels were increased significantly beyond 100 years of age, were negatively associated with diabetes prevalence, and were associated with SNVs in (p=2.21 × 10 ) and (p=5.72 × 10 ). Multivariate regression analysis revealed that genetic variants, BMI, and high-density lipoprotein cholesterol (HDLC) were the main factors associated with cHMW adiponectin levels in the very old, whereas the BMI showed no association in centenarians. The hazard ratios for all-cause mortality in the intermediate and high cHMW adiponectin groups in very old men were significantly higher rather than those for all-cause mortality in the low-level cHMW adiponectin group, even after adjustment with BMI. In contrast, the hazard ratios for all-cause mortality were significantly higher for high cHMW adiponectin groups in very old women, but were not significant after adjustment with BMI. cHMW adiponectin levels increased with age until centenarians, and the contribution of known major factors associated with cHMW adiponectin levels, including BMI and HDLC, varies with age, suggesting that its physiological significance also varies with age in the oldest old. This study was supported by grants from the Ministry of Health, Welfare, and Labour for the Scientific Research Projects for Longevity; a Grant-in-Aid for Scientific Research (No 21590775, 24590898, 15KT0009, 18H03055, 20K20409, 20K07792, 23H03337) from the Japan Society for the Promotion of Science; Keio University Global Research Institute (KGRI), Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan Science and Technology Agency (JST) Research Complex Program \"Tonomachi Research Complex\" Wellbeing Research Campus: Creating new values through technological and social innovation (JP15667051), the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development (No. 16kk0205009h001, 17jm0210051h0001, 19dk0207045h0001); the medical-welfare-food-agriculture collaborative consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries; and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology.