Applications of physical exercise in frailty: Progress, mechanisms, and prospects
Abstract
Frailty is a kind of clinical state or a kind of complex pathological syndromes characterized by impaired physiological functions, weakened physical and mental resistance to stress, and reduced ability to maintain homeostasis in multiple systems. Several types of risk factors can affect the occurrence and development of frailty either independently or in conjunction with one another, including age, gender, and exercise habits; and the multidimensional systemic treatment are often required to alleviate or improve frailty. Physical exercise is the various kinds of systematic and conscious activities, it has been demonstrated that regular exercise can promote the normal metabolism processes within the body, thereby preventing or alleviating the symptoms of various diseases. Physical exercise has the potential to regulate oxidative stress, immune response, and endocrine balance in the body of frail people by activating multiple signaling pathways including mitochondrial function, cytokine secretion, and regulation of inflammatory factors, its applications in frailty has been made the significant progress and the underlying mechanisms has been further elucidated. In this review, we have summarized the recent progress on the applications of physical exercise in frailty and the potential mechanisms, hoping that our reviews may provide some helpful guidance for the further research.
References
1. Irina Savelieva, Stefano Fumagalli, Rose Anne Kenny, Stefan Anker, Athanase Benetos, Giuseppe Boriani, et al. EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA). Europace, 2023, 25(4): 1249–1276.
2. O’Caoimh R, Galluzzo L, Rodríguez-Laso Á, Van der Heyden J, Ranhoff AH, Lamprini-Koula M, et al. Prevalence of frailty at population level in European ADVANTAGE Joint Action Member States: a systematic review and meta-analysis. Ann Ist Super Sanita, 2018, 54:226–238.
3. Ma L, Tang Z, Zhang L, et al. Prevalence of frailty and associated factors in the community-dwelling population of china. J Am Geriatr Soc, 2018, 66(3): 559-564.
4. He B, Ma Y, Wang C, et al. Prevalence and risk factors for frailty among community-dwelling older people in china: a systematic review and meta-analysis. J Nutr Health Aging, 2019, 23(5): 442-450.
5. Liang YD, Zhang YN, Li YM, et al. Identification of frailty and its risk factors in elderly hospitalized patients from different wards: a cross-sectional study in china. Clin Interv Aging, 2019, 14: 2249-2259.
6. Dent E, Martin FC, Bergman H, Woo J, Romero-Ortuno R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet, 2019, 394(10206): 1376-1386.
7. Carl I Cohen, Rivka Benyaminov, Manumar Rahman, Dilys Ngu, Michael Reinhardt. Frailty: A Multidimensional Biopsychosocial Syndrome. Med Clin North Am, 2023, 107(1): 183-197.
8. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health.
9. Paddy C Dempsey, Alex V Rowlands, Tessa Strain, Francesco Zaccardi, Nathan Dawkins, Cameron Razieh, et al. Physical activity volume, intensity, and incident cardiovascular disease. Eur Heart J, 2022, 43(46):4789-4800.
10. Qiaoyun Wanga,Wenli Zhou. Roles and molecular mechanisms of physical exercise in cancer prevention and treatment. J Sport Health Sci., 2021, 10(2): 201-210.
11. Sargent L, Nalls M, Singleton A, Palta P, Kucharska-Newton A, Pankow J, et al. Moving towards the detection of frailty with biomarkers: A population health study. Aging Cell. 2024, 23(2):e14030.
12. Veronese N, Custodero C, Cella A, Demurtas J, Zora S, Maggi S, et al. Prevalence of multidimensional frailty and pre-frailty in older people in different settings: A systematic review and meta-analysis. Ageing Res Rev., 2021, 72:101498.
13. Gielen E, Dupont J, Dejaeger M, Laurent MR. Sarcopenia, osteoporosis and frailty. Metabolism, 2023, 145:155638.
14. He D, Wang Z, Li J, Yu K, He Y, He X, et al. Changes in frailty and incident cardiovascular disease in three prospective cohorts. Eur Heart J, 2024, 45(12):1058-1068.
15. Zheng Z, Lv Y, Rong S, Sun T, Chen L. Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease. JAMA Neurol., 2023, 80(5):455-461.
16. Salaffi F, Di Matteo A, Farah S, Di Carlo M. Inflammaging and Frailty in Immune-Mediated Rheumatic Diseases: How to Address and Score the Issue. Clin Rev Allergy Immunol., 2023, 64(2):206-221.
17. Karakousis ND, Biliou S, Pyrgioti EE, Georgakopoulos PN, Liakopoulos V, Papanas N. Frailty, sarcopenia and diabetic kidney disease: where do we stand? Int Urol Nephrol., 2023, 55(5):1173-1181.
18. Cesari M, Prince M, Thiyagarajan JA, et al. Frailty: An emerging public health priority. J Am Med Dir Assoc., 2016, 17 (3):188-192.
19. Walston J, Hadley EC, FerrucciL, et al. Research agenda for frailty in older adults：toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc., 2006, 54(6): 991- 1001.
20. Calvani R, Marini F, Cesari M, et al. Biomarkers for physical frailty and sarcopenia：state of the science and future developments. J Cachexia Sarcopenia Muscle, 2015, 6(4): 278- 286.
21. Zekun Zheng, Yanling Lv, Shuang Rong, Taoping Sun, Liangkai Chen. Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease. JAMA Neurol., 2023, 80(5):455-461.
22. Jinhui Zhou, Xinwei Li, Xiang Gao, Yuan Wei, Lihong Ye, Sixin Liu, et al. Leisure Activities, Genetic Risk, and Frailty: Evidence from the Chinese Adults Aged 80 Years or Older. Gerontology, 2023, 69(8):961-971.
23. Lucia Galluzzo, Marianna Noale, Stefania Maggi, Alessandro Feraldi, Marzia Baldereschi, Antonio Di Carlo, et al. Frailty Prevalence, Incidence, and Association with Incident Disability in the Italian Longitudinal Study on Aging. Gerontology, 2023, 69(3):249-260.
24. Nicolas Sirven, Magali Dumontet, Thomas Rapp. The dynamics of frailty and change in socio-economic conditions: evidence for the 65+ in Europe. Eur J Public Health, 2020, 30(4):715-719.
25. Fangqing Li, Yike Yan, Lei Zheng, Chenming Wang, Xin Guan, Shiru Hong, et al. Frailty and its combined effects with lifestyle factors on cognitive function: a cross-sectional study. BMC Geriatr., 2023, 23: 79.
26. Dhamoon MS, Cheung YK, Moon Y, DeRosa J, Sacco R, Elkind MS, et al. Cerebral white matter disease and functional decline in older adults from the Northern Manhattan Study: a longitudinal cohort study. PLoS Med., 2018,15: e1002529.
27. Kant IM, Mutsaerts HJ, van Montfort SJ, Jaarsma-Coes MG, Witkamp TD, Winterer G, et al. The association between frailty and MRI features of cerebral small vessel disease. Sci Rep, 2019, 9: 11343.
28. Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K. The association between sedentary behaviour, moderate–vigorous physical activity and frailty in NHANES cohorts. Maturitas, 2015, 80: 187–191.
29. Aiello A, Farzaneh F, Candore G, Caruso C, Davinelli S, Gambino CM, Ligotti ME, Zareian N, Accardi G. Immunosenescence and its hallmarks: how to oppose aging strategically? A review of potential options for therapeutic intervention. Front Immunol., 2019,10: 2247.
30. Arnardottir NY, Koster A, Domelen DR, Brychta RJ, Caserotti P, Eiriksdottir G, et al. Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study. Behav Brain Res., 2016, 296: 118–124.
31. Kant IM, de Bresser J, van Montfort SJ, Aarts E, Verlaan JJ, Zacharias N, et al. BioCog Consortium. The association between brain volume, cortical brain infarcts, and physical frailty. Neurobiol Aging, 2018, 70: 247–253.
32. Sayed N, Huang Y, Nguyen K, Krejciova-Rajaniemi Z, Grawe AP, Gao T, et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging, 2021, 1:598-615.
33. Javier Angulo, Mariam El Assar, Alejandro Álvarez-Bustos, and Leocadio Rodríguez-Mañas. Physical activity and exercise: Strategies to manage frailty. Redox Biol., 2020, 35: 101513.
34. Zanotto T, Mercer TH, van der Linden ML, Rush R, Traynor JP, Petrie CJ, et al. The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: a prospective cohort study. BMC Nephrol., 2020, 21(1):99.
35. Lee SY, Nyunt MSZ, Gao Q, Gwee X, Chua DQL, Yap KB, et al. Association of Tai Chi exercise with physical and neurocognitive functions, frailty, quality of life and mortality in older adults: Singapore Longitudinal Ageing Study. Age Ageing, 2022, 51(4): afac086.
36. Liao CD, Chen HC, Huang SW, Liou TH. The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials. Nutrients, 2019, 11(8):1713.
37. Keating N, Coveney C, McAuliffe FM, Higgins MF. Aerobic or Resistance Exercise for Improved Glycaemic Control and Pregnancy Outcomes in Women with Gestational Diabetes Mellitus: A Systematic Review. Int J Environ Res Public Health, 2022, 19(17):10791.
38. Katrina L Piercy, Richard P Troiano, Rachel M Ballard, Susan A Carlson, Janet E Fulton, Deborah A Galuska, et al. The Physical Activity Guidelines for Americans. JAMA, 2018, 320(19):2020-2028.
39. Sabine Schootemeijer, Nicolien M van der Kolk, Bastiaan R Bloem, Nienke M de Vries. Current Perspectives on Aerobic Exercise in People with Parkinson’s Disease. Neurotherapeutics, 2020, 17(4):1418-1433.
40. Elise S Bisset, Stefan Heinze-Milne, Scott A Grandy, and Susan E Howlett, Rozalyn M Anderson. Aerobic Exercise Attenuates Frailty in Aging Male and Female C57Bl/6 Mice and Effects Systemic Cytokines Differentially by Sex. J Gerontol A Biol Sci Med Sci., 2022, 77(1): 41–46.
41. Elizabeth C Lefferts, Esmée A Bakker, Salvatore Carbone, Carl J Lavie, Duck-Chul Lee. Associations of total and aerobic steps with the prevalence and incidence of frailty in older adults with hypertension. Prog Cardiovasc Dis., 2021, 67:18-25.
42. Yu-Jie Zhang, Yao Yao, Pei-Dong Zhang, Zhi-Hao Li, Pei Zhang, Fu-Rong Li, et al. Association of regular aerobic exercises and neuromuscular junction variants with incidence of frailty: an analysis of the Chinese Longitudinal Health and Longevity Survey. J Cachexia Sarcopenia Muscle., 2021, 12(2):350-357.
43. Wei-Han Weng, Yun-Hui Cheng, Tzu-Hsin Yang, Shwn-Jen Lee, Yea-Ru Yang, Ray-Yau Wang. Effects of strength exercises combined with other training on physical performance in frail older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr., 2022, 102:104757.
44. Sigve N Aas, Daniel Tømmerbakke, Sindre Godager, Martin Nordseth, Andrea Armani, Marco Sandri, et al. Effects of acute and chronic strength training on skeletal muscle autophagy in frail elderly men and women. Exp Gerontol., 2020, 142:111122.
45. Kerri M. Winters-Stone, Sydnee Stoyles, Nathan Dieckmann, Elizabeth Eckstrom, Shiuh-Wen Luoh, Fay Horak, et al. an strength training or tai ji quan training reduce frailty in postmenopausal women treated with chemotherapy? A secondary data analysis of the GET FIT trial. Res Sq. Preprint, 2023. doi: 10.21203/rs.3.rs-3425168/v1.
46. Ivan Baltasar-Fernandez, Hector Soto-Paniagua, Julian Alcazar, María Isabel Uceta Espinosa, Luis M Alegre, Francisco José Gracía-García, et al. Long-term effects of a 6-week power-based resistance training and fast walking interval training program on physical function, muscle power, disability and frailty in pre-frail and frail older adults. Gerontology, 2024. doi: 10.1159/000536363.
47. Khow KSF, Visvanathan R. Falls in the Aging Population. Clin Geriatr Med. 2017;33(3):357–368.
48. Juliana N.A. Costa, Alexandre L.A. Ribeiro, Daniele B.G. Ribeiro, Silvia G.R. Neri, Daniel F. Barbosa, Bruna P. Avelar, et al. Balance Exercise Circuit for fall prevention in older adults: a randomized controlled crossover trial. J Frailty Sarcopenia Falls, 2022, 7(2): 60–71.
49. S Karagül, S Kibar, S Ay, D Evcik, S Ergin. The effect of a 6-week balance exercise program on balance parameters in frailty syndrome: a randomized controlled, double-blind, prospective study.Georgian Med News, 2023, (345):37-42.
50. Liu NY. Getting qi and arrival of qi. Zhongguo Zhen Jiu, 2014, 34(8):828-830.
51. X Wan, J Shen, G He. Effects of Traditional Chinese Exercises on Frailty, Quality of Life, and Physical Function on Frail and Pre-Frail Older People: A Systematic Review and Meta-Analysis. J Frailty Aging, 2022, 11(4):407-415.
52. Cheng ZJ, Zhang SP, Gu YJ, Chen ZY, Xie FF, Guan C, et al. Effectiveness of Tuina Therapy Combined With Yijinjing Exercise in the Treatment of Nonspecific Chronic Neck Pain: A Randomized Clinical Trial. JAMA Netw Open, 2022, 5(12): e2246538.
53. Deuel LM, Seeberger LC. Complementary Therapies in Parkinson Disease: a Review of Acupuncture, Tai Chi, Qi Gong, Yoga, and Cannabis. Neurotherapeutics, 2020, 17(4):1434-1455.
54. Li F, Harmer P, Fitzgerald K, et al. Effectiveness of a therapeutic Tai Ji Quan intervention vs a multimodal exercise intervention to prevent falls among older adults at high risk of falling: a randomized clinical trial. JAMA Intern Med. 2018;178(10):1301-1310.
55. Gong X, Rong G, Wang Z, Zhang A, Li X, Wang L. Baduanjin exercise for patients with breast cancer: A systematic review and meta-analysis. Complement Ther Med, 2022, 71:102886.
56. Rui Xia, Mingyue Wan, Huiying Lin, Pingting Qiu, Yu Ye, Jianquan He, et al. Effects of a traditional Chinese mind–body exercise, Baduanjin, on the physical and cognitive functions in the community of older adults with cognitive frailty: study protocol for a randomised controlled trial. BMJ Open, 2020, 10(4): e034965.
57. Xiaoqian Wang, Jiawei Wu, Haoran Zhang, Guohua Zheng. Effect of Baduanjin exercise on executive function in older adults with cognitive frailty: A randomized controlled trial. Clin Rehabil., 2024, 38(4):510-519.
58. Z Jiayuan, J Xiang-Zi, M Li-Na, Y Jin-Wei, Y Xue. Effects of Mindfulness-Based Tai Chi Chuan on Physical Performance and Cognitive Function among Cognitive Frailty Older Adults: A Six-Month Follow-Up of a Randomized Controlled Trial. J Prev Alzheimers Dis., 2022, 9(1):104-112.
59. Nor Fadila Kasim, Jet Veldhuijzen van Zanten, Sarah Aldred. Tai Chi is an effective form of exercise to reduce markers of frailty in older age. Exp Gerontol., 2020, 135:110925.
60. Uratcha Sadjapong, Supachai Yodkeeree, Somporn Sungkarat, Penprapa Siviroj. Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial. Int J Environ Res Public Health, 2020, 17(11):3760.
61. Jiraporn Chittrakul, Penprapa Siviroj, Somporn Sungkarat, Ratana Sapbamrer. Multi-System Physical Exercise Intervention for Fall Prevention and Quality of Life in Pre-Frail Older Adults: A Randomized Controlled Trial. Int J Environ Res Public Health, 2020, 17(9):3102.
62. Cordes T, Bischoff LL, Schoene D, Schott N, Voelcker-Rehage C, Meixner C, et al. A multicomponent exercise intervention to improve physical functioning, cognition and psychosocial well-being in elderly nursing home residents: a study protocol of a randomized controlled trial in the PROCARE (prevention and occupational health in long-term care) project. BMC Geriatr., 2019, 19(1):369.
63. Ambarish Pandey, Dalane W Kitzman, M Benjamin Nelson, Amy M Pastva, Pamela Duncan, David J Whellan, et al. Frailty and Effects of a Multidomain Physical Rehabilitation Intervention Among Older Patients Hospitalized for Acute Heart Failure: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol., 2023, 8(2):167-176.
64. Lenore Dedeyne, Jolan Dupont, Katrien Koppo, Sabine Verschueren, Jos Tournoy, Evelien Gielen. Exercise and Nutrition for Healthy AgeiNg (ENHANce) project - effects and mechanisms of action of combined anabolic interventions to improve physical functioning in sarcopenic older adults: study protocol of a triple blinded, randomized controlled trial. BMC Geriatr., 2020, 20(1): 532.
65. Ambarish Pandey, Matthew W Segar, Sumitabh Singh, Gordon R Reeves, Christopher O’Connor, Ileana Piña, et al. Frailty Status Modifies the Efficacy of Exercise Training Among Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the HF-ACTION Trial. Circulation, 2022, 146(2):80-90.
66. Xiaoxing Lai, Lin Bo, Hongwei Zhu, Baoyu Chen, Zhao Wu, Hongdi Du, et al. Effects of lower limb resistance exercise on muscle strength, physical fitness, and metabolism in pre-frail elderly patients: a randomized controlled trial. BMC Geriatr., 2021, 21(1):447.
67. Francesco Carli, Guillaume Bousquet-Dion, Rashami Awasthi, Noha Elsherbini, Sender Liberman, Marylise Boutros, et al. Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer: A Randomized Clinical Trial. JAMA Surg., 2020, 155(3):233-242.
68. M Wei, S He, D Meng, G Yang, Z Wang. Hybrid Exercise Program Enhances Physical Fitness and Reverses Frailty in Older Adults: Insights and Predictions from Machine Learning. J Nutr Health Aging, 2023, 27(10):894-902.
69. Alison M Mudge, Anita Pelecanos, Julie A Adsett. Frailty implications for exercise participation and outcomes in patients with heart failure. J Am Geriatr Soc., 2021, 69(9):2476-2485.
70. Daniel I McIsaac, Emily Hladkowicz, Gregory L Bryson, Alan J Forster, Sylvain Gagne, Allen Huang, et al. Home-based prehabilitation with exercise to improve postoperative recovery for older adults with frailty having cancer surgery: the PREHAB randomised clinical trial. Br J Anaesth., 2022, 129(1):41-48.
71. Pei-Shiun Chang, Yvonne Lu, Chi Mai Nguyen, Youngnok Suh, Mary Luciani, Susan Ofner, et al. Effects of Qigong Exercise on Physical and Psychological Health among African Americans. West J Nurs Res., 2021, 43(6):551-562.
72. L F Tan, Y H Chan, S Seetharaman, A Denishkrshna, L Au, S C Kwek, et, al. Impact of Exercise and Cognitive Stimulation Therapy on Physical Function, Cognition and Muscle Mass in Pre-Frail Older Adults in the Primary Care Setting: A Cluster Randomized Controlled Trial. J Nutr Health Aging., 2023, 27(6):438-447.
73. Ruby Yu, Grace Leung, Jean Woo. Randomized Controlled Trial on the Effects of a Combined Intervention of Computerized Cognitive Training Preceded by Physical Exercise for Improving Frailty Status and Cognitive Function in Older Adults. Int J Environ Res Public Health, 2021, 18(4):1396.
74. Chia-Pei Chou, Kuei-Min Chen, Hsiao-Ting Tung, Frank Belcastro, Hui-Fen Hsu. Physical fitness and frailty status of frail older adults in long-term care facilities after acupunch exercises: A cluster-randomized controlled trial. Exp Gerontol., 2022, 163:111799.
75. Jack Quach, Olga Theou, Mario U Pérez-Zepeda, Judith Godin, Kenneth Rockwood, Dustin S Kehler. Effect of a physical activity intervention and frailty on frailty trajectory and major mobility disability. J Am Geriatr Soc., 2022, 70(10):2915-2924.
76. Ruth Teh, Daniel Barnett, Richard Edlin, Ngaire Kerse, Debra L Waters, Leigh Hale, et al. Effectiveness of a complex intervention of group-based nutrition and physical activity to prevent frailty in pre-frail older adults (SUPER): a randomised controlled trial. Lancet Healthy Longev., 2022, 3(8):e519-e530.
77. Asuka Tani,Shinsuke Mizutani, Hiro Kishimoto, Saori Oku, Kiyomi Iyota, Tianshu Chu, et al. The Impact of Nutrition and Oral Function Exercise on among Community-Dwelling Older People. Nutrients, 2023, 15(7): 1607.
78. Cristina Flor-Rufino, Joaquín Barrachina-Igual, Pilar Pérez-Ros, Ana Pablos-Monzó, Francisco Miguel Martínez-Arnau. Resistance training of peripheral muscles benefits respiratory parameters in older women with sarcopenia: Randomized controlled trial. Arch Gerontol Geriatr., 2023, 104:104799.
79. M Gagesch, M Wieczorek, B Vellas, R W Kressig, R Rizzoli, J Kanis, W C Willett, et al. Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial. J Frailty Aging, 2023, 12(1):71-77.
80. John Travers, Roman Romero-Ortuno, John Langan, Fergal MacNamara, Darren McCormack, Christopher McDermott, Jude McEntire, et al. Building resilience and reversing frailty: a randomised controlled trial of a primary care intervention for older adults. Age Ageing, 2023, 52(2):afad012.
81. Carlo Custodero, Pasquale Agosti, Stephen D Anton, Todd M Manini, Madia Lozupone, Francesco Panza, et al. Effect of Physical Activity Intervention on Gait Speed by Frailty Condition: A Randomized Clinical Trial. J Am Med Dir Assoc., 2023, 24(4):489-496.
82. Guilherme Eustáquio Furtado, Humberto Moreira Carvalho, Marisa Loureiro, Miguel Patrício, Matheus Uba-Chupel, Juan C Colado, et al. Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes. Exp Gerontol., 2020, 130:110790.
83. Sara A Suikkanen, Paula K Soukkio, Eeva M Aartolahti, Hannu Kautiainen, Sanna M Kääriä, Markku T Hupli, et al. Effects of Home-Based Physical Exercise on Days at Home and Cost-Effectiveness in Pre-Frail and Frail Persons: Randomized Controlled Trial. J Am Med Dir Assoc., 2021, 22(4):773-779.
84. Koichiro Matsuo, Norie Kito, Koichi Ogawa, Ayako Izumi, Masako Kishima, Masataka Itoda, et al. Improvement of oral hypofunction by a comprehensive oral and physical exercise programme including textured lunch gatherings. J Oral Rehabil., 2021, 48(4):411-421.
85. Sara Suikkanen, Paula Soukkio, Hannu Kautiainen, Sanna Kääriä, Markku T Hupli, Sarianna Sipilä, Kaisu Pitkälä, et al. Changes in the Severity of Frailty Among Older Adults After 12 Months of Supervised Home-Based Physical Exercise: A Randomized Clinical Trial. J Am Med Dir Assoc., 2022, 23(10):1717.e9-1717.e15.
86. Natália Boneti Moreira, André L F Rodacki, Sabrine N Costa, Arthur Pitta, Paulo C B Bento. Perceptive-Cognitive and Physical Function in Prefrail Older Adults: Exergaming Versus Traditional Multicomponent Training. Rejuvenation Res., 2021, 24(1):28-36.
87. Ilkem Guzel, Filiz Can. The effects of different exercise types on cognitive and physical functions in dementia patients: A randomized comparative study. Arch Gerontol Geriatr., 2024, 119:105321.
88. Sara Suikkanen, Paula Soukkio, Eeva Aartolahti, Sanna Kääriä, Hannu Kautiainen, Markku T Hupli, et al. Effect of 12-Month Supervised, Home-Based Physical Exercise on Functioning Among Persons With Signs of Frailty: A Randomized Controlled Trial. Arch Phys Med Rehabil., 2021, 102(12):2283-2290.
89. Eva Román, Naujot Kaür, Elisabet Sánchez, Maria Poca, Josep Padrós, Maria Josep Nadal, et al. Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial. Hepatol Commun., 2024, 8(5):e0443.
90. Ana Moradell, Ángel I Fernández-García, David Navarrete-Villanueva, Jorge Pérez-Gómez, Eva Gesteiro, Ignacio Ara Royo, et al. Does nutritional status influence the effects of a multicomponent exercise programme on body composition and physical fitness in older adults with limited physical function? Eur J Sport Sci., 2023, 23(7):1375-1384.
91. Isabel B Rodrigues, Justin B Wagler, Heather Keller, Lehana Thabane, Zachary J Weston, Sharon E Straus, et al. Encouraging older adults with pre-frailty and frailty to “MoveStrong”: an analysis of secondary outcomes for a pilot randomized controlled trial. Health Promot Chronic Dis Prev Can., 2022, 42(6):238-251.
92. Wonil Park, Jaesung Lee, Kwangseok Hong, Hun-Young Park, Saejong Park, Nahyun Kim, et al. Protein-Added Healthy Lunch-Boxes Combined with Exercise for Improving Physical Fitness and Vascular Function in Pre-Frail Older Women: A Community-Based Randomized Controlled Trial. Clin Interv Aging., 2023, 18:13-27.
93. Yosuke Osuka, Hiroyuki Sasai, Narumi Kojima, Masamitsu Sugie, Keiko Motokawa, Kazushi Maruo, et al. 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., 2023, 23(1):32-37.
94. Rosie Fountotos, Sandra Lauck, Nicolo Piazza, Giuseppe Martucci, Rakesh Arora, Anita Asgar, et al. Protein and Exercise to Reverse Frailty in Older Men and Women Undergoing Transcatheter Aortic Valve Replacement: Design of the PERFORM-TAVR Trial. Can J Cardiol., 2024, 40(2):267-274.
95. Keiichi Kojima, Haruna Ishikawa, Shinji Watanabe, Naohisa Nosaka, Tatsushi Mutoh. A Randomized, Double-Blind, Controlled Trial Assessing If Medium-Chain Triglycerides in Combination with Moderate-Intensity Exercise Increase Muscle Strength in Healthy Middle-Aged and Older Adults. Nutrients, 2023, 15(14):3275.
96. Noritake Hirota, Hiroshi Okada, Noboru Okamura. The effectiveness in preventing frailty of exercise intervention provided by community pharmacists to older persons with chronic conditions: A pragmatic randomized controlled trial. BMC Geriatr., 2023, 23(1):225.
97. Sara Mollà-Casanova, Elena Muñoz-Gómez, Núria Sempere-Rubio, Marta Inglés, Marta Aguilar-Rodríguez, Álvaro Page, et al. Effect of virtual running with exercise on functionality in pre-frail and frail elderly people: randomized clinical trial. Aging Clin Exp Res., 2023, 35(7): 1459–1467.
98. Chad Yixian Han, Yogesh Sharma, Alison Yaxley, Claire Baldwin, Richard Woodman, Michelle Miller. Individualized Hospital to Home, Exercise-Nutrition Self-Managed Intervention for Pre-Frail and Frail Hospitalized Older Adults: The INDEPENDENCE Randomized Controlled Pilot Trial.
99. Szu-Yun Wu, Yu-Yao Cheng, Hsing-Yi Chang, Pei-Hsuan Wang, I-Ching Hsieh, Nai-Hua Yeh, Kuo-Chin Huang, et al. Efficacy of Dietary Intervention with Group Activities on Dietary Intakes, Frailty Status, and Working Memory: A Cluster-Randomized Controlled Trial in Community Strongholds. Nutrients, 2023, 15(8):1976.
100. S E R Lim, S J Meredith, S Agnew, E Clift, K Ibrahim, H C Roberts. Volunteer-led online group exercise for community-dwelling older people: a feasibility and acceptability study. BMC Geriatr, 2023, 23(1):461.
101. Ilkem Guzel 1, Filiz Can. The effects of different exercise types on cognitive and physical functions in dementia patients: A randomized comparative study. Arch Gerontol Geriatr. 2024, 119:105321.
102. omán E, Kaür N, Sánchez E, Poca M, Padrós J, Nadal MJ, et al. Home exercise, branched-chain amino acids, and probiotics improve frailty in cirrhosis: A randomized clinical trial. Hepatol Commun, 2024, 8(5):e0443.
103. Lin YJ, Hsu WC, Wang KC, Tseng WY, Liao YY. Interactive boxing-cycling on frailty and activity limitations in frail and prefrail older adults: A randomized controlled trial. Ann Phys Rehabil Med., 2024, 67(4):101819.
104. Ángel Iván Fernández-García, Alba Gómez-Cabello, Alejandro Gómez-Bruton, Ana Moradell, David Navarrete-Villanueva, Jorge Pérez-Gómez, et al. Effects of multicomponent training and detraining on the fitness of older adults with or at risk of frailty: results of a 10-month quasi-experimental study. Eur J Sport Sci., 2023, 23(8):1696-1709.
105. Xiaoxing Lai, Hongwei Zhu, Zhao Wu, Baoyu Chen, Qian Jiang, Hongdi Du, et al. Dose-response effects of resistance training on physical function in frail older Chinese adults: A randomized controlled trial. J Cachexia Sarcopenia Muscle, 2023,14(6):2824-2834.
106. B Chen, M Li, H Zhao, R Liao, J Lu, J Tu, et al. Effect of Multicomponent Intervention on Functional Decline in Chinese Older Adults: A Multicenter Randomized Clinical Trial. J Nutr Health Aging., 2023, 27(11):1063-1075.
107. Yee-Lam E Chan, Wang-Sheng Lin, Hui-Chen Lai, Chih-Yuan Hung, Mao-Hsuan Huang. Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty. Asia Pac Psychiatry., 2024, 16(2):e12556.
108. Sylvie Belleville, M Cuesta, M Bieler-Aeschlimann, K Giacomino, A Widmer, A G Mittaz Hager, et al. Pre-frail older adults show improved cognition with StayFitLonger computerized home-based training: a randomized controlled trial. Geroscience, 2023, 45(2):811-822.
109. Justina Y W Liu, Yue-Heng Yin, Patrick P K Kor, Rick Y C Kwan, Paul H Lee, Wai Tong Chien, et al. Effects of an individualised exercise programme plus Behavioural Change Enhancement (BCE) strategies for managing fatigue in frail older adults: a cluster randomised controlled trial. BMC Geriatr., 2023, 23(1):370.
110. Wajeeha Sahar, Mehwish Waseem, Muhammad Riaz, Nouman Nazeer, Muhammad Ahmad, Zulfiqar Haider. Effects of prehabilitation resistance training in mild to moderate clinically frail patients awaiting coronary artery bypass graft surgery. J Investig Med., 2024, 72(1):151-158.
111. Ivan Baltasar-Fernandez, Jose Losa-Reyna, Aitor Carretero, Carlos Rodriguez-Lopez, Ana Alfaro-Acha, Amelia Guadalupe-Grau, et al. Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD. Scand J Med Sci Sports, 2023, 33(9):1661-1676.
112. Robert G Memelink, Rose Njemini, Minse J J de Bos Kuil, Suzan Wopereis, Johan de Vogel-van den Bosch, Josje D Schoufour, et al. The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes. Exp Gerontol., 2024, 190:112410.
113. Kaja Kircher, Oliver Chaudry, Armin M Nagel, Mansour Ghasemikaram, Michael Uder, Franz Jakob, et al. Effects of high-intensity training on fatty infiltration in paraspinal muscles in elderly males with osteosarcopenia - the randomized controlled FrOST study. BMC Geriatr., 2024, 24(1):141.
114. Xiaohong Zhang, Cees Peter van der Schans, Yanhui Liu, Wilhelmus Petrus Krijnen, Johannes Simon Maria Hobbelen. Efficacy of Dance Intervention for Improving Frailty Among Chinese Older Adults Living in the Community: A Randomized Controlled Trial. J Aging Phys Act., 2023, 31(5):806-814.
115. A B Bays-Moneo, M Izquierdo, M M Antón, E L Cadore. Cost-Consequences Analysis Following Different Exercise Interventions in Institutionalized Oldest Old: A Pilot Study of a Randomized Clinical Trial. J Nutr Health Aging., 2023, 27(11):1091-1099.
116. Fermín García-Gollarte, Ania Mora-Concepción, Sacramento Pinazo-Hernandis, Eva Segura-Ortí, Juan José Amer-Cuenca, María Dolores Arguisuelas-Martínez, et al. Effectiveness of a Supervised Group-Based Otago Exercise Program on Functional Performance in Frail Institutionalized Older Adults: A Multicenter Randomized Controlled Trial. J Geriatr Phys Ther., 2023, 46(1):15-25.
117. Bridgitte Swales, Gemma C Ryde, Anna C Whittaker. A Mixed Methods Feasibility Study of Machine-Based Resistance Training With Prefrail Older Adults in Residential Care: The Keeping Active in Residential Elderly Trial II. J Aging Phys Act., 2024, 32(2):244-263.
118. Shan-Che Woo, Miao-Yen Chen, Liang-Kung Chen, Chieh-Yu Liu. Effectiveness of Resistance Band Use in Conjunction With Tai Chi Among Older Adults With Prefrailty to Improve Functional Fitness, Quality of Life, and Heart Rate Variability. J Gerontol Nurs., 2024, 50(5):19-26.
119. Luo J, Mills K, le Cessie S, Noordam R, van Heemst D. Ageing, age-related diseases and oxidative stress: What to do next? Ageing Res Rev. 2020, 57:100982.
120. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature, 2000, 408(6809):239-247.
121. Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza E, et al. An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int J Mol Sci., 2022, 23(11):5938.
122. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol., 2023, 97(10):2499-2574.
123. Karen Kich Gomes, Ana Beatriz Dos Santos, Jaciana Sousa Dos Anjos, Luana Paganotto Leandro, Maria Takemura Mariano, Felipe Lima Pinheiro, et al. Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster. Oxid Med Cell Longev., 2023, 2023:7222462.
124. Si-Yue Chen, Tong-Yao Wang, Chao Zhao, Hui-Jing Wang. Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome. World J Gastroenterol., 2022, 28(38): 5547–5556.
125. Han H, Jiang Y, Wang M, Melaku M, Liu L, Zhao Y, Everaert N, Yi B, Zhang H. Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut-liver axis. Crit Rev Food Sci Nutr. 2021:1–18.
126. Yue Wu, Siqi Cheng, Shaoyuan Lei, Dongxiao Li, Zhongzhong Li, Yansu Guo. The Association Between the Composite Dietary Antioxidant Index and Frailty Symptoms: Mediating Effects of Oxidative Stress. Clin Interv Aging., 2024, 19:163-173.
127. Marcelo Paes de Barros, André Luís Lacerda Bachi, Juliana de Melo Batista Dos Santos, Rafael Herling Lambertucci, Rafael Ishihara, Tatiana Geraldo Polotow, et al. The poorly conducted orchestra of steroid hormones, oxidative stress and inflammation in frailty needs a maestro: Regular physical exercise. Exp Gerontol., 2021, 155:111562.
128. Beatrice Arosio, Evelyn Ferri, Daniela Mari, Eleonora Tobaldini, Giovanni Vitale, Nicola Montano. The influence of inflammation and frailty in the aging continuum. Mech Ageing Dev., 2023, 215:111872.
129. Maria Cybularz, Sandy Wydra, Katharina Berndt, David M Poitz, Peggy Barthel, Ahmad Alkouri, et al. Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations. Exp Gerontol., 2021, 149:111317.
130. Qi Zhang, Ziwen Wang, Mengmeng Song, Tong Liu, Jiashan Ding, Li Deng, et al. Effects of systemic inflammation and frailty on survival in elderly cancer patients: Results from the INSCOC study. Front Immunol., 2023, 14:936904.
131. Kaleen M Lavin, Ryan K Perkins, Bozena Jemiolo, Ulrika Raue, Scott W Trappe, Todd A Trappe. Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation in women. J Appl Physiol (1985)., 2020, 129(6):1493-1504.
132. Singh A, Schurman SH, Bektas A, Kaileh M, Roy R, et al. Aging and Inflammation. Cold Spring Harb Perspect Med., 2024, 14(6):a041197.
133. Diego Marcos-Pérez, Sara Cruces-Salguero, Esther García-Domínguez, Marcos J Araúzo-Bravo, Mari Carmen Gómez-Cabrera, José Viña, et al. Physical Interventions Restore Physical Frailty and the Expression of CXCL-10 and IL-1β Inflammatory Biomarkers in Old Individuals and Mice. Biomolecules, 2024, 14(2):166.
134. Tsuyoshi Sasaki, Eijiro Yamada, Ryota Uehara, Shuichi Okada, Hirotaka Chikuda, and Masanobu Yamada. Role of Fyn and the interleukin-6-STAT-3-autophagy axis in sarcopenia. iScience, 2023, 26(10): 107717.
135. David Sebastián, Marc Beltrà, Andrea Irazoki, David Sala, Pilar Aparicio, Cecilia Aris, et al. TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging. Autophagy, 2024, 1-10.
136. Li-Kung Wu, Surbhi Agarwal, Chia-Hua Kuo, Yen-Lun Kung, Cecilia Hsuan Day, Pi-Yu Lin, et al. Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson’s disease. Phytomedicine, 2022, 104:154250.
137. Zhengzhong Zeng, Jiling Liang, Liangwen Wu, Hu Zhang, Jun Lv, and Ning Chen. Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control. Front Physiol., 2020, 11: 583478.
138. Zhiwei Li, Hua Lv, Xiaoli Cui, Wei Di, Xiansong Cheng, Jun Liu, et al. Exercise attenuates mitochondrial autophagy and neuronal degeneration in MPTP induced Parkinson’s disease by regulating inflammatory pathway. Folia Neuropathol., 2023, 61(4):426-432.
139. Wenxian Zhou, Yifeng Shi, Hui Wang, Linjie Chen, Caiyu Yu, Xufei Zhang, et al. Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy. Exp Mol Med., 2022, 54(7):1038-1048.
140. Kenta Kuramoto, Huijia Liang, Jung-Hwa Hong, Congcong He. Exercise-activated hepatic autophagy via the FN1-α5β1 integrin pathway drives metabolic benefits of exercise. Cell Metab., 2023, 35(4):620-632.e5.
141. A Vallet, N Del Campo, E O Hoogendijk, A Lokossou, O Balédent, Z Czosnyka, et al. Biomechanical response of the CNS is associated with frailty in NPH-suspected patients. J Neurol., 2020, 267(5):1389-1400.
142. Sophie Guillotin, Alexandra Vallet, Sylvie Lorthois, Philippe Cestac, Eric Schmidt, Nicolas Delcourt, et al. Association Between Homocysteine, Frailty and Biomechanical Response of the CNS in NPH-Suspected Patients. J Gerontol A Biol Sci Med Sci., 2022, 77(7):1335-1343.
143. Benoit Gobron, Malory Couchot, Nigel Irwin, Erick Legrand, Béatrice Bouvard, Guillaume Mabilleau. Development of a First-in-Class Unimolecular Dual GIP/GLP-2 Analogue, GL-0001, for the Treatment of Bone Fragility. J Bone Miner Res., 2023, 38(5):733-748.
144. Jana Maria Hommen, João P Batista, L Cornelius Bollheimer, Frank Hildebrand, Thea Laurentius, Hannah Lena Siebers. Movement patterns during gait initiation in older adults with various stages of frailty: a biomechanical analysis. Eur Rev Aging Phys Act., 2024, 21(1):1.
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