Published papers

Atherosclerosis, a major contributor to cardiovascular diseases (CVD), remains a leading cause of global mortality and morbidity. The pathogenesis of atherosclerosis involves a complex interplay of endothelial dysfunction, chronic inflammation, lipid accumulation, and arterial stiffness. Among the various preventive strategies, physical activity has emerged as a highly effective, non-pharmacological intervention. This review examines the preventive effects of different types of exercise-specifically aerobic exercise, resistance training, and combined training-on atherosclerosis development. Drawing on evidence from landmark studies, we explore the underlying mechanisms by which these exercise modalities improve endothelial function, reduce systemic inflammation, and enhance lipid profiles, thereby mitigating the progression of atherosclerosis. Additionally, the review discusses the dose-response relationship between physical activity and cardiovascular health, the differential effects of exercise intensities, and the potential risks associated with high-intensity training. The synergistic benefits of combined aerobic and resistance training are highlighted, particularly in populations with metabolic syndrome or other high-risk conditions. Emerging trends in personalized exercise medicine and the use of wearable technology for monitoring physical activity are also addressed, underscoring the potential for tailored exercise prescriptions to maximize cardiovascular health. By integrating current research findings, this review provides insights into effective exercise strategies for reducing cardiometabolic risk and emphasizes the importance of personalized approaches in exercise interventions.

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-025-06308-7.

© The Author(s) 2018. Background: In older persons, lower hand grip strength is associated with poorer cognition. Little is known about how the rate of muscle contraction relates to cognition and upper extremity motor function, and sex differences are understudied. Methods: Linear regression, adjusting for age, race, education, body mass index, appendicular lean mass, and knee pain, assessed sex-specific cross-sectional associations of peak torque, rate of torque development (RTD), and rate of velocity development (RVD) with cognition and upper extremity motor function. Results: In men (n = 447), higher rate-adjusted peak torque and a greater RVD were associated with faster simple finger tapping speed, and a greater RVD was associated with higher nondominant pegboard performance. In women (n = 447), higher peak torque was not associated with any measures, but a greater RTD was associated with faster simple tapping speed and higher language performance, and a greater RVD was associated with higher executive function, attention, memory, and nondominant pegboard performance. In women with low isokinetic peak torque, RVD was associated with attention and memory. Conclusions: RVD capacity may reflect neural health, especially in women with low muscle strength.

© The Authors 2018. Objective 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.Design 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.Setting Tokyo, the capital prefecture of Japan.Subjects Eighty very old Japanese (thirty-six men and forty-four women) aged 82-94 years.Results 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.Conclusions 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.

Background: The pathophysiological mechanisms underlying the association between red blood cell distribution width (RDW) and all-cause mortality are unknown. We conducted a data-driven discovery investigation to identify plasma proteins that mediate the association between RDW and time to death in community-dwelling adults. Methods: At baseline, 962 adults (women, 54·4%; age range, 21–98 years) participated in the InCHIANTI, “Aging in the Chianti Area” study, and proteomics data were generated from their plasma specimens. Of these, 623 participants had proteomics data available at the 9-year follow-up. For each visit, a total of 1301 plasma proteins were measured using SOMAscan technology. Complete data on vital status were available up to the 15-year follow-up period. Protein-specific exponential distribution accelerated failure time, and linear regression analyses adjusted for possible covariates were used for mortality and mediation analyses, respectively (survival data analysis). Findings: Baseline values of EGFR, GHR, NTRK3, SOD2, KLRF1, THBS2, TIMP1, IGFBP2, C9, APOB, and LRP1B mediated the association between baseline RDW and all-cause mortality. Changes in IGFBP2 and C7 over 9 years mediated the association between changes in RDW and 6-year all-cause mortality. Interpretation: Cellular senescence may contribute to the association between RDW and mortality. Funding: This study was funded by grants from the National Institutes of Health (NIH) and the National Institute on Aging (NIA) contract and was supported by the Intramural Research Program of the NIA, NIH. The InCHIANTI study was supported as a ‘targeted project’ by the Italian Ministry of Health and in part by the U.S. NIA.

Purpose: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. Methods: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. Results: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. Conclusions: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders Background: Slow gait speed is a powerful predictor of disability in activities of daily living and mortality. Muscle strength and body composition change over time, but their changes differ by sex. How these parameters jointly affect gait speed decline is unknown. Understanding this association could help develop and evaluate the sex-specific effects of lifestyle interventions to delay gait speed decline in older adults. We assessed whether changes in strength (Δstrength), appendicular lean mass (ΔALM), and fat mass (Δfat) jointly relate to change in gait speed and whether the association differs by sex. Methods: The analytic sample comprised 575 women and 539 men aged 22–95 years enrolled in the Baltimore Longitudinal Study of Aging. Mean follow-up was 4.0 years. Measures included isometric knee extension strength, dual-energy X-ray absorptiometry-assessed ALM and fat mass, and gait speed from the 400 m fast pace walk. Sex-specific linear mixed models were adjusted for follow-up time and baseline age, race, height, ALM, fat mass, peak torque, and gait speed. We also included second-order interaction terms of the key predictive variables (e.g. Δstrength × ΔALM). To interpret the interactions, we estimated average gait declines using the 25th or 75th percentile of the two significant predictive variables and then assessed which condition relates to larger decline in gait speed. Results: In both sexes, independent of ΔALM and Δfat, larger decline in strength significantly related to larger decline in gait speed (P = 0.01 for both sexes). In men, interactions between Δstrength × ΔALM and Δfat by ΔALM were associated with change in gait speed; men with greater declines in both muscle strength and ALM or greater declines in both ALM and fat have steeper gait speed decline. In contrast, in women, the interaction between Δfat and ΔALM was associated with change in gait speed; women with an increase in fat mass combined with less decline in ALM have steeper gait speed decline. Conclusions: While change in strength affects change in gait speed in both sexes, the effects of body composition change differ by sex. Dual-energy X-ray absorptiometry-based estimates of lean mass may be confounded by intramuscular fat. Future studies should examine sex-specific combined effects of change in strength and body composition on mobility using multiple techniques to measure body composition. Intervention studies should consider testing sex-specific interventions on body composition.

Published 2018. This article is a U.S. Government work and is in the public domain in the USA. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders Background: With aging, the ability to generate muscle force decreases, contributing to declines in physical functions such as walking. While most studies assess muscle force by peak torque, the rate of torque development (RTD) reflects a dynamic component of muscle performance that is important for physical function. Using data from the Baltimore Longitudinal Study of Aging, we assessed whether RTD adds significantly to peak torque in associations with lower extremity performance. If so, RTD may help identify weak older adults for screening and intervention. Methods: We assessed associations of RTD and peak torque with physical performance independent of demographics, BMI, body composition, and each other in 1089 Baltimore Longitudinal Study of Aging participants (49.7% women; aged 26 to 96 years; women, 64.0 ± 13.8 years; men, 68.4 ± 14.4 years). Peak torque was assessed by isometric and 30 deg/s isokinetic knee extension tests. Peak RTD was operationalized as the maximum torque-time slope among successive 50 ms epochs over the first 3 s of a test of knee extension isometric strength, with the knee joint positioned at 120 deg of flexion. A battery of lower extremity performance tests included gait speed during a 6 m walk at usual and fast pace (6 m usual and fast), time to complete a 400 m walk at fast pace (400 m), distance covered in a 2.5 min walk at normal pace (2.5 min), time to complete 5 and 10 chair stands, and two summary tests of lower extremity performance. Sex-stratified generalized linear regression models were adjusted for age, race, BMI, appendicular lean mass, and whole body fat mass. Results: In men, independent of either measure of peak torque and cofactors, RTD was a significant (P < 0.05) predictor of all lower extremity performance tests except the 400 m and 2.5 min walks. In women, independent of peak torque, RTD was only a significant independent correlate of the 6 m fast walk (P < 0.001). Conclusions: RTD independently contributes to physical functions in men but less in women. The mechanisms underlying the sex difference are unclear and require further study.

Background: Muscle strength and brain volume decline with aging; changes in the brain manifested as change in volume may play a role in age-related strength loss, but this hypothesis has never been tested longitudinally. We examined longitudinal associations between brain volume changes and knee extension peak torque change in participants of the Baltimore Longitudinal Study of Aging. Methods: Brain volumes and isokinetic concentric knee extension peak torque at 30 deg/s were measured in 678 participants (55.2% women; baseline age, 50.1-97.2 years; median follow-up time in those who visited two or more times (n = 375, 4.0 [interquartile range {IQR}, 2.3-5.0] years). Correlations between longitudinal changes in brain volumes and knee extension peak torque were examined using bivariate linear mixed-effects models, adjusted for baseline age, sex, race, education, and intracranial volume. Results: Greater decline in muscle strength was associated with greater atrophies in global gray matter, temporal lobe, frontal gray matter, temporal gray matter, superior frontal gyrus, inferior frontal gyrus, supramarginal gyrus, middle temporal gyrus, inferior temporal gyrus, and occipital pole (r ranging from. 30 to. 77, p <. 05). After multiple comparison adjustment, only larger decrease in middle temporal gyrus remained significantly related to larger decrease in muscle strength (q = 0.045). Conclusions: In older adults, declines in knee extension muscle strength co-occurred with atrophies in frontal, temporal, and occipital gray matter. These findings support the idea that age-related knee extension muscle strength is linked with atrophy in some specific brain regions related to motor control.

© 2019 The American Geriatrics Society BACKGROUND: Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. DESIGN: Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). SETTING: NIA IRP Clinical Research Unit, Baltimore, MD. PARTICIPANTS: Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. MEASUREMENTS: Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. RESULTS: In linear regression models, higher τPCr was associated with older age (standardized β =.39; P <.001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τPCr (βage =.22; P <.001) and had a smaller standardized regression coefficient than MVPA (βMVPA = −.33; P <.001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (βage =.20; P =.003), while the standardized coefficient for MVPA decreased only 3% (βMVPA = −.32; P <.001). CONCLUSION: Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695–1699, 2019.

Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. We examined the relationship between plasma GDF-15 concentrations at baseline in 708 nonanemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased the risk of developing anemia (hazards ratio 1.15, 95% confidence interval 1.09, 1.21, p < .0001) compared to those in the lower 3 quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Circulating GDF-15 is an independent predictor for the development of anemia in older adults.