Frailty and Musculoskeletal Health Research

Members

Keywords

Frailty, sarcopenia, dynapenia, cognitive function, dementia, diabetes mellitus, chronic pain, malnutrition, polypharmacy, potentially inappropriate medication, fall prevention, physical activity, sedentary behavior, sleep, muscle strength, handgrip strength, knee extensor strength, bioelectrical impedance analysis, phase angle, biomarker, metabolomics, glycomics, cell-free DNA, mobile health (mHealth), smartphone app, wearable devices, smartwatch, exercise intervention, Radio Calisthenics, randomized controlled trial, cohort study

Major Research Titles

1. Maintenance and expansion of a community-based cohort of older adults
2. Determinants, health consequences, and intervention strategies for frailty
3. Biomarkers, diagnostic methods, and intervention strategies for sarcopenia
4. Factors associated with transitions from mild cognitive impairment to normal cognition or dementia
5. Development of fall risk assessment tools for older workers

Research summary

１．Maintenance and expansion of a community-based cohort of older adults

Our research group has continuously maintained and operated two large community-based cohorts of older adults: the Otasha Study 2017/2019 Cohort and the Itabashi Longitudinal Study on Aging. A distinctive feature of these cohorts is that participants are invited to visit our institute, where we collect precise longitudinal data through direct measurements of various functions and the collection of biological specimens. As a valuable source of high-quality data in Japan, these cohorts provide a key research infrastructure for geriatric research.
Specifically, the cohorts have accumulated cross-disciplinary data on more than 1,000 variables, including physical function, cognitive function, blood and urine biomarkers, body composition, nutritional status, and psychosocial factors. In addition, we have established an ongoing system for collecting serum, plasma, and urine samples, thereby providing a high-quality research platform that supports multidimensional analyses spanning basic, clinical, and epidemiological research. This data infrastructure has supported a wide range of projects both within and beyond our institute.
Through this research theme, we aim to generate and disseminate findings continuously by leveraging these high-quality cohort data and to produce scientific evidence that supports frailty prevention and the extension of healthy life expectancy in older adults.

2．Determinants, health consequences, and intervention strategies for frailty

Building on the community-based cohorts described above, our research group is working to clarify the multifactorial determinants of frailty and to develop effective intervention approaches. To identify its determinants and consequences, we conduct detailed analyses of associations not only with physical function, such as knee extensor strength and gait performance, but also with polypharmacy, potentially inappropriate medications, malnutrition, and sleep, as well as physiological biomarkers including metabolites assessed by metabolomics and cell-free DNA. Through these efforts, we aim to improve the early detection of frailty and deepen understanding of its underlying pathophysiology.
In terms of intervention strategies, we are evaluating the effects of a Radio Calisthenics-based intervention through a randomized controlled trial, focusing on physical function and quality of life in frail older adults. We are also introducing mobile health (mHealth) technology through a smartphone application and advancing the development of a behavior change program designed to increase daily physical activity and enhance participation in social activities. Through these efforts, we seek to establish a comprehensive, evidence-based strategy for frailty prevention.

3．Biomarkers, diagnostic methods, and intervention strategies for sarcopenia

Our research group is conducting advanced studies aimed at the early diagnosis and pathophysiological understanding of sarcopenia, as well as the development of effective intervention strategies. In the area of diagnostic development, we examine the validity of phase angle and skeletal muscle mass assessed by bioelectrical impedance analysis (BIA), and we are working to establish highly accurate predictive equations that can be applied in clinical settings. We also pursue the identification of minimally invasive next-generation biomarkers through a multifaceted approach, including analyses of cell-free DNA (cfDNA) in blood and urine, together with metabolomic and glycomic profiling. These efforts are laying the groundwork for the objective assessment of muscle quality and biological ageing.
With regard to intervention strategies, we promote an approach that combines exercise with nutritional and food-derived components. As part of an ongoing collaborative study with a private-sector company, we are conducting a randomized controlled trial to examine the combined effects of nicotinamide mononucleotide (NMN), which has potential anti-ageing properties, and strength training. In addition to detailed evaluation of changes in skeletal muscle mass using CT imaging, we are carrying out multidimensional assessments of blood biomarkers, sleep, cognitive function, and physical activity. Through these efforts, we aim to develop intervention strategies that contribute to improvements in sarcopenia and quality of life.

4．Factors associated with transitions from mild cognitive impairment to normal cognition or dementia

Our research group, in collaboration with the Integrated Research Initiative for Living Well with Dementia (IRIDE), is leading a large-scale observational study, the DEMCIRC Study, in partnership with other research groups to identify factors associated with the onset of mild cognitive impairment (MCI), as well as reversion to normal cognition and progression to dementia. In this flagship project, we recruit a broad spectrum of community-dwelling older adults, ranging from cognitively normal individuals to those with MCI, from the community-based cohorts managed by our group, and conduct a long-term follow-up study that includes detailed cognitive assessments, brain imaging using MRI and PET, and comprehensive health evaluations.
Leveraging our well-established community-based cohorts of older adults, a major strength of our group, we perform integrated analyses of physical function, biological specimens, and lifestyle factors to examine the effects of declining physical function, malnutrition, and sleep disturbances on transitions in cognitive status. Through the accumulation of this multidimensional evidence, we aim to develop targeted interventions and preventive strategies to delay the onset of dementia and promote reversion to normal cognition.

5．Development of fall risk assessment tools for older workers

Our research group addresses the social challenges posed by the growing number of older adults who wish to remain in the workforce by developing fall risk assessment tools and prevention strategies specifically for older workers. We examine not only age-related changes in physical function, such as muscle strength and balance, but also work-related factors, as well as the effects of sensory impairment, medical conditions, and medication use on fall risk, using a multidimensional analytical approach. We are evaluating the validity of screening methods that can be readily implemented in workplace settings. Through this work, we aim to identify modifiable risk factors for preventing work-related falls among older workers and to propose appropriate approaches to continued employment based on individual physical condition, together with effective workplace intervention programs. Ultimately, we seek to establish an evidence-based risk management model that supports a society in which older workers can continue working safely and remain active in the workforce.

Notable publications (from 2020)

1. Kojima N, Osuka Y, Motokawa K, Edahiro A, Hirano H, Awata S, Sasai H. Factors associated with being perceived as vocally young in older adults. J Voice. (in press)
2. Yoshida Y, Shida T, Yonamine M, Osuka Y, Takekoshi K, Sasai H. Blood and urine cell-free circulating DNA in older adults with sarcopenia: a hypothesis-generating study. Eur Geriatr Med. (in press)
3. Daimaru K, Kojima N, Hatanaka S, Ohta T, Osuka Y, Sasai H, Obuchi SP, Murayama H, Okamura T, Hirata T, Suzuki H, Fujiwara Y, Iwata A, Awata S, Toba K, Akishita M; IRIDE Cohort Study investigators. Diabetes as a potential contributor to dynapenia in community-dwelling older adults in Japan: sex- and age-specific cross-sectional findings from the Integrated Research Initiative for Living Well With Dementia Cohort Study. Geriatr Gerontol Int. 26(3):e70422, 2026.3.
4. Nishimoto J, Deguchi N, Hatanaka S, Shida T, Ohta T, Kojima N, Shirobe M, Motokawa K, Hirano H, Okamura T, Awata S, Sasai H. Association between pro-inflammatory dietary patterns and chronic pain in community-dwelling older adults: a cross-sectional study. Arch Gerontol Geriatr. 140:106035, 2026.1.
5. Tsushima H, Shida T, Hatanaka S, Ohta T, Kojima N, Sasai H, Sugimoto M. Associations between serum pigment epithelium-derived factor and physical performance in older women: the Otassha study. PLoS One. 20(12):e0338884, 2025.12.
6. Osuka Y, Hatanaka S, Kojima N, Shida T, Ohta T, Motokawa K, Edahiro A, Shirobe M, Iwasaki M, Hirano H, Awata S, Sasai H. Is appendicular lean soft tissue mass a clinically valid diagnostic marker for sarcopenia? Geriatr Gerontol Int. 25(12):1840-1845, 2025.12.
7. Azuma K, Osuka Y, Kojima N, Shida T, Ohta T, Ogawa S, Sasai H, Inoue S. Vitamin K insufficiency predicts cognitive decline in community-dwelling older adults: the Otassha study. Geriatr Gerontol Int. 25(12):1971-1973, 2025.12.
8. Kojima N, Osuka Y, Sasai H, Shinkai S, Ishii K, Kohda N, Kobayashi Y, Kim H. Lower Firmicutes abundance in gut microbiota associated with amyloid-β positivity in older adults in Japan as assessed by positron emission tomography. PLoS One. 20(10):e0332801, 2025.10.
9. Shida T, Hatanaka S, Kojima N, Ohta T, Maruo K, Osuka Y, Sasai H. Identification of metabolites associated with the development of sarcopenia in older women: a longitudinal nested case-control study. Clin Nutr ESPEN. 69:133-139, 2025.10.
10. Ohta T, Kojima N, Hatanaka S, Shida T, Osuka Y, Sasai H. Value of muscle strength in improving the predictive capability for cognitive decline in older women by established risk factors: a prospective cohort study in the Otassha study. J Alzheimers Dis. 106(3):978-987, 2025.8.
11. Shimura H, Okada S, Maruo K, Daimaru K, Deguchi N, Fujiwara Y, Sasai H. Agreement between TDK Silmee W22 and ActiGraph wGT3X-BT for estimating daily step counts and moderate to vigorous physical activity in free-living adults: comparative study. JMIR Form Res. 9:e64602, 2025.7.
12. Daimaru K, Hatanaka S, Osuka Y, Kojima N, Maruo K, Sasai H. Association of potentially inappropriate medications with frailty and frailty components in community-dwelling older women in Japan: the Otassha study. Geriatr Gerontol Int. 25(5):686-693, 2025.5.
13. Shimura H, Okada S, Daimaru K, Deguchi N, Fujiwara Y, Sasai H. Concurrent validity of the Japanese version of the International Physical Activity Questionnaire long form for assessing walking behavior across adulthood: applicability to older adults. Cureus. 17(3):e81328, 2025.3.
14. Shimura H, Okada S, Maruo K, Daimaru K, Deguchi N, Fujiwara Y, Sasai H. Comparison of Omron and ActiGraph monitors in estimating daily step counts and time spent in moderate to vigorous physical activity in free-living adults. BMJ Open Sport Exerc Med. 11(1):e002402, 2025.3.
15. Shida T, Hatanaka S, Kojima N, Ohta T, Osuka Y, Maruo K, Sasai H. Association of serum metabolites with frailty phenotype and its components: a cross-sectional case-control study. Biogerontology. 26(1):21, 2024.12.
16. Hatanaka S, Shida T, Osuka Y, Kojima N, Motokawa K, Okamura T, Hirano H, Awata S, Sasai H. Association between phase angle and inflammatory blood biomarkers in community-dwelling older adults: Itabashi Longitudinal Study on Aging. Clin Nutr ESPEN. 64:114-121, 2024.12.
17. Osuka Y, Kojima N, Daimaru K, Ono R, Sugie M, Omura T, Motokawa K, Ueda T, Maruo K, Aoyama T, Inoue S, Sasai H. Effects of Radio-Taiso on health-related quality of life in older adults with frailty: a randomized controlled trial. J Epidemiol. 34(10):467-476, 2024.10.
18. Ohta T, Kojima N, Osuka Y, Sasai H. Physical frailty predicts cognitive decline among community-dwelling older Japanese women: a prospective cohort study from the Otassha study. Arch Gerontol Geriatr. 124:105453, 2024.9.
19. Suzuki T, Osuka Y, Kojima N, Sasai H, Nakamura K, Oba C, Sasaki M, Kim H. Association between the intake/type of cheese and cognitive function in community-dwelling older women in Japan: a cross-sectional cohort study. Nutrients. 16(16):2800, 2024.8.
20. Shida T, Hatanaka S, Ohta T, Osuka Y, Kojima N, Motokawa K, Iwasaki M, Miyamae F, Okamura T, Hirano H, Awata S, Sasai H. Proposal and validation of an equation to identify sarcopenia using bioelectrical impedance analysis-derived parameters. Nutrition. 124:112453, 2024.8.
21. Ohta T, Kojima N, Osuka Y, Sasai H. Knee extensor muscle strength associated with the onset of depression in older Japanese women: the Otassha study. Nutrients. 16(14):2179, 2024.7.
22. Ohta T, Osuka Y, Shida T, Daimaru K, Kojima N, Maruo K, Iizuka A, Kitago M, Fujiwara Y, Sasai H. Feasibility, acceptability, and potential efficacy of a mobile health application for community-dwelling older adults with frailty and pre-frailty: a pilot study. Nutrients. 16(8):1181, 2024.4.
23. Shida T, Yoshida Y, Ohta T, Kojima N, Osuka Y, Takekoshi K, Sasai H. Identification of a novel biomarker for sarcopenia diagnosis using serum metabolomic analysis: a pilot study. Eur Geriatr Med. 15(2):571-577, 2024.4.
24. Daimaru K, Osuka Y, Kojima N, Mizukami K, Motokawa K, Iwasaki M, Inagaki H, Miyamae F, Okamura T, Hirano H, Awata S, Sasai H. Associations of polypharmacy with frailty severity and each frailty phenotype in community-dwelling older adults: Itabashi Longitudinal Study on Aging. Geriatr Gerontol Int. 24(Suppl 1):196-201, 2024.3.
25. Hatanaka S, Sasai H, Shida T, Osuka Y, Kojima N, Ohta T, Abe T, Yamashita M, Obuchi SP, Ishizaki T, Fujiwara Y, Awata S, Toba K; IRIDE Cohort Study investigators. Association between dynapenia and cognitive decline in community-dwelling older Japanese adults: the IRIDE Cohort Study. Geriatr Gerontol Int. 24(Suppl 1):123-129, 2024.3.
26. Hatanaka S, Osuka Y, Kojima N, Motokawa K, Hayakawa M, Mikami Y, Iwasaki M, Inagaki H, Miyamae F, Okamura T, Hirano H, Awata S, Sasai H. Relationship between phase angle and lower-extremity function in older adults: Itabashi Longitudinal Study on Aging. Nutrition. 119:112289, 2024.3.
27. Deguchi N, Osuka Y, Kojima N, Motokawa K, Iwasaki M, Inagaki H, Miyamae F, Okamura T, Hirano H, Awata S, Sasai H. Questionnaire for medical checkup of old-old is non-inferior to the Kihon Checklist in screening frailty among independent older adults aged 75 years and older: the Itabashi Longitudinal Study on Aging. Geriatr Gerontol Int. 24(Suppl 1):176-181, 2024.3.
28. Deguchi N, Osuka Y, Kojima N, Motokawa K, Iwasaki M, Inagaki H, Miyamae F, Okamura T, Hirano H, Awata S, Sasai H. Sex-specific factors associated with acceptance of smartwatches among urban older adults: the Itabashi longitudinal study on aging. Front Public Health. 12:1261275, 2024.2.
29. Azuma K, Osuka Y, Kojima N, Sasai H, Inoue S. Vitamin K insufficiency predicts incidence of frailty in community-dwelling older adults: the Otassha study. J Bone Miner Metab. 41(6):817-821, 2023.11.
30. Wakaba K, Osuka Y, Kojima N, Sasai H. Predictive capability of 5 sarcopenia diagnostic criteria for fall incidents in older Japanese women: the Otassha study. J Am Med Dir Assoc. 24(10):1549-1554, 2023.10.
31. Kim H, Osuka Y, Kojima N, Sasai H, Nakamura K, Oba C, Sasaki M, Suzuki T. Inverse association between cheese consumption and lower cognitive function in Japanese community-dwelling older adults based on a cross-sectional study. Nutrients. 15(14):3181, 2023.7.
32. Osuka Y, Takeshima N, Kojima N, Kohama T, Fujita E, Kusunoki M, Imai A, Kitabayashi Y, Brechue WF, Sasai H. Qualitative assessment of standing motion with Kinect™ is a useful additional diagnostic marker for sarcopenia. Arch Gerontol Geriatr. 108:104915, 2023.5.
33. Ohta T, Sasai H, Osuka Y, Kojima N, Abe T, Yamashita M, Obuchi SP, Ishizaki T, Fujiwara Y, Awata S, Toba K; IRIDE Cohort Study Investigators. Age- and sex-specific associations between sarcopenia severity and poor cognitive function among community-dwelling older adults in Japan: the IRIDE Cohort Study. Front Public Health. 11:1148404, 2023.4.
34. Osuka Y, Sasai H, Kojima N, Sugie M, Motokawa K, Maruo K, Ono R, Aoyama T, Inoue S, Kim H. Adherence, safety and potential effectiveness of a home-based Radio-Taiso exercise program in older adults with frailty: a pilot randomized controlled trial. Geriatr Gerontol Int. 23(1):32-37, 2023.1.
35. Deguchi N, Kojima N, Osuka Y, Sasai H. Factors associated with passive sedentary behavior among community-dwelling older women with and without knee osteoarthritis: the Otassha study. Int J Environ Res Public Health. 19(21):13765, 2022.10.
36. Osuka Y, Kojima N, Sugie M, Omura T, Motokawa K, Ueda T, Maruo K, Ono R, Aoyama T, Inoue S, Kim H, Sasai H. Effects of a home-based Radio-Taiso exercise programme on health-related quality of life in older adults with frailty: protocol for an assessor-blind randomised controlled trial. BMJ Open. 12(9):e063201, 2022.9.
37. Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S. Association of vitamin K insufficiency as evaluated by serum undercarboxylated osteocalcin with depressive symptoms in community-dwelling older adults. Am J Geriatr Psychiatry. 30(9):1051-1052, 2022.9.
38. Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S. Association of vitamin K insufficiency as evaluated by serum undercarboxylated osteocalcin with frailty in community-dwelling older adults. Front Aging. 3:865178, 2022.4.
39. Osuka Y, Kojima N, Nishihara K, Sasai H, Wakaba K, Tanaka K, Kim H. β-hydroxy-β-methylbutyrate supplementation may not enhance additional effects of exercise on muscle quality in older women. Med Sci Sports Exerc. 54(4):543-550, 2022.4.
40. Osuka Y, Okubo Y, Nofuji Y, Sasai H, Seino S, Maruo K, Fujiwara Y, Oka H, Shinkai S, Lord SR, Kim H. Modifiable intrinsic factors related to occupational falls in older workers. Geriatr Gerontol Int. 22(4):338-343, 2022.4.
41. Azuma K, Osuka Y, Kojima N, Sasai H, Kim H, Inoue S. Association of vitamin K insufficiency with cognitive dysfunction in community-dwelling older adults. Front Nutr. 8:811831, 2022.1.
42. Osuka Y, Nofuji Y, Seino S, Maruo K, Oka H, Shinkai S, Fujiwara Y, Sasai H. The effect of a multicomponent intervention on occupational fall-related factors in older workers: a pilot randomized controlled trial. J Occup Health. 64(1):e12374, 2022.1.
43. Osuka Y, Kojima N, Sasai H, Wakaba K, Miyauchi D, Tanaka K, Kim H. Effects of exercise and/or β-hydroxy-β-methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in older women with low muscle mass: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 114(4):1371-1385, 2021.10.
44. Osuka Y, Kojima N, Sasai H, Ohara Y, Watanabe Y, Hirano H, Kim H. Exercise types and the risk of developing cognitive decline in older women: a prospective study. J Alzheimers Dis. 77(4):1733-1742, 2020.10.