Frailty syndrome and the crucial role of lifestyle modification in prevention and dismantling the “frailty phenotype”
DOI:
https://doi.org/10.12775/QS.2026.68.74429Keywords
aging, frailty, frailty syndrome, elderly, older, civilisation, inflammaging, lifestyle, lifestyle modification, diet, physical activity, aerobic training, resistance training, polypharmacology, multimorbidity, geriatricsAbstract
Background: Frailty syndrome represents a profound state of increased physiological vulnerability driven by the multisystemic erosion of homeostatic resilience, distinct from mere chronological aging. As the global population ages, recognizing and managing this complex clinical entity has become a paramount challenge in geriatric and internal medicine.
Aim: To synthesize current evidence regarding the pathophysiological mechanisms underpinning frailty, evaluate diagnostic frameworks, and outline optimal clinical management strategies, with a distinct emphasis on pharmacological stewardship and targeted lifestyle medicine interventions.
Evidence Synthesis: The biological core of frailty is driven by "inflammaging," neuroendocrine dysregulation, and cellular senescence, which collectively precipitate profound anabolic resistance, sarcopenia, and dynapenia. Diagnostically, the syndrome requires a multidimensional approach utilizing the Comprehensive Geriatric Assessment (CGA). Within clinical management, diminished physiological reserves and altered pharmacokinetics severely amplify the risks of polypharmacy. Crucially, targeted lifestyle interventions remain the only validated strategies to actively reverse the frail phenotype. Progressive resistance training effectively provides the mechanical loading necessary to stimulate myofibrillar synthesis, while precision nutrition directly overrides age-related anabolic resistance and attenuates systemic inflammation.
Conclusions: Optimizing care for frail older adults requires a fundamental paradigm shift from disease-centric treatment models to holistic, function-preserving strategies. By minimizing cumulative pharmacological burden and aggressively implementing evidence-based physical and nutritional therapies, clinicians can successfully replenish depleted physiological reserves, alter the trajectory of biological decline, and sustain the patient's functional autonomy.
References
[1] Kones R, Rumana U. Cardiometabolic diseases of civilization: History and maturation of an evolving global threat. An update and call to action. Annals of Medicine 2017;49:260–74. https://doi.org/10.1080/07853890.2016.1271957.
[2] Cohen CI, Benyaminov R, Rahman M, Ngu D, Reinhardt M. Frailty: A Multidimensional Biopsychosocial Syndrome. The Medical Clinics of North America 2023;107:183–97. https://doi.org/10.1016/j.mcna.2022.04.006.
[3] Fried L, Tangen C, Walston J, Newman A, Hirsch C, Gottdiener J, et al. Frailty in Older Adults: Evidence for a Phenotype. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2001. https://pubmed.ncbi.nlm.nih.gov/11253156/ (accessed July 18, 2026).
[4] Rockwood K, Mitnitski A. Frailty in Relation to the Accumulation of Deficits. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2007;62:722–7. https://doi.org/10.1093/gerona/62.7.722.
[5] Frontera WR. Physiologic Changes of the Musculoskeletal System with Aging. Physical Medicine and Rehabilitation Clinics of North America 2017;28:705–11. https://doi.org/10.1016/j.pmr.2017.06.004.
[6] Gawrońska K, Lorkowski J. Falls, Aging and Public Health - a Literature Review. Ortopedia, Traumatologia, Rehabilitacja 2020;22:397–408. https://doi.org/10.5604/01.3001.0014.6044.
[7] Everitt AV. The Neuroendocrine System and Aging. Gerontology 1980;26:108–19. https://doi.org/10.1159/000212403.
[8] Fulop T, Larbi A, Pawelec G, Khalil A, Cohen AA, Hirokawa K, et al. Immunology of Aging: the Birth of Inflammaging. Clinical Reviews in Allergy & Immunology 2021:1–14. https://doi.org/10.1007/s12016-021-08899-6.
[9] Mangoni AA, Jackson SHD. Age-related Changes in Pharmacokinetics and pharmacodynamics: Basic Principles and Practical Applications. British Journal of Clinical Pharmacology 2004;57:6–14. https://doi.org/10.1046/j.1365-2125.2003.02007.x.
[10] Hanlon P, Nicholl BI, Jani BD, Lee D, McQueenie R, Mair FS. Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants. The Lancet Public Health 2018;3:e323–32. https://doi.org/10.1016/s2468-2667(18)30091-4.
[11] Kim J, Parish AL. Polypharmacy and Medication Management in Older Adults. Nursing Clinics of North America 2017;52:457–68. https://doi.org/10.1016/j.cnur.2017.04.007.
[12] Cresswell KM, Fernando B, McKinstry B, Sheikh A. Adverse drug events in the elderly. British Medical Bulletin 2007;83:259–74. https://doi.org/10.1093/bmb/ldm016.
[13] Covinsky KE, Palmer RM, Fortinsky RH, Counsell SR, Stewart AL, Kresevic D, et al. Loss of Independence in Activities of Daily Living in Older Adults Hospitalized with Medical Illnesses: Increased Vulnerability with Age. Journal of the American Geriatrics Society 2003;51:451–8. https://doi.org/10.1046/j.1532-5415.2003.51152.x.
[14] American Geriatrics Society. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society 2023;71. https://doi.org/10.1111/jgs.18372.
[15] Oliveira RMAF de, Gorzoni ML, Rosa RF. Potentially inappropriate medication use in hospitalized elderly patients. Revista Da Associação Médica Brasileira 2022;68:797–801. https://doi.org/10.1590/1806-9282.20220015.
[16] Singh A, Schurman SH, Bektas A, Kaileh M, Roy R, Wilson DM, et al. Aging and Inflammation. Cold Spring Harbor Perspectives in Medicine 2023:a041197. https://doi.org/10.1101/cshperspect.a041197.
[17] Birch J, Gil J. Senescence and the SASP: many therapeutic avenues. Genes & Development 2020;34:1565–76. https://doi.org/10.1101/gad.343129.120.
[18] Vanitallie TB. Frailty in the elderly: contributions of sarcopenia and visceral protein depletion. Metabolism: Clinical and Experimental 2003;52:22–6. https://doi.org/10.1016/s0026-0495(03)00297-x.
[19] Schippinger W. Comprehensive Geriatric Assessment. Wiener Medizinische Wochenschrift 2022;172. https://doi.org/10.1007/s10354-021-00905-y.
[20] Rodrigues F, Domingos C, Monteiro D, Morouço P. A Review on Aging, Sarcopenia, Falls, and Resistance Training in Community-Dwelling Older Adults. International Journal of Environmental Research and Public Health 2022;19:874. https://doi.org/10.3390/ijerph19020874.
[21] Delaire L, Courtay A, Humblot J, Aubertin-Leheudre M, Mourey F, Racine AN, et al. Implementation and Core Components of a Multimodal Program including Exercise and Nutrition in Prevention and Treatment of Frailty in Community-Dwelling Older Adults: A Narrative Review. Nutrients 2023;15:4100. https://doi.org/10.3390/nu15194100.
[22] Warren JL, Hunter GR, Gower BA, Bamman MM, Windham ST, Moellering DR, et al. Exercise Effects on Mitochondrial Function and Lipid Metabolism during Energy Balance. Medicine & Science in Sports & Exercise 2019:1. https://doi.org/10.1249/mss.0000000000002190.
[23] Shah IA, Ishaq S, Lee S- Da, Wu B-T. Effects of Exercise Training on Cardiac Mitochondrial Functions in Diabetic Heart: A Systematic Review. International Journal of Molecular Sciences 2024;26:8. https://doi.org/10.3390/ijms26010008.
[24] Margolis LM, Pasiakos SM. Optimizing Intramuscular Adaptations to Aerobic Exercise: Effects of Carbohydrate Restriction and Protein Supplementation on Mitochondrial Biogenesis. Advances in Nutrition 2013;4:657–64. https://doi.org/10.3945/an.113.004572.
[25] Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, et al. Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults. JAMA 2014;311:2387. https://doi.org/10.1001/jama.2014.5616.
[26] Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, et al. Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: a Position Paper from the PROT-AGE Study Group. Journal of the American Medical Directors Association 2013;14:542–59. https://doi.org/10.1016/j.jamda.2013.05.021.
[27] Héctor Fuentes-Barría, Raúl Aguilera-Eguía, Lissé Angarita-Davila, Rojas-Gómez D, Alarcón-Rivera M, López-Soto O, et al. Vitamin D and Sarcopenia: Implications for Muscle Health. Biomedicines 2025;13:1863–3. https://doi.org/10.3390/biomedicines13081863.
[28] Zheng Z, Xu W, Wang F, Qiu Y, Xue Q. Association between vitamin D3 levels and frailty in the elderly: A large sample cross-sectional study. Frontiers in Nutrition 2022;9. https://doi.org/10.3389/fnut.2022.980908.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Marcel Majewski, Bogumił Libura, Martyna Lazar, Łukasz Szkaradowski, Szymon Baranowski, Julia Lewańska, Krzysztof Bogdański, Zuzanna Kruszyńska, Anastasiya Aleshchyk, Michał Adamczak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 75
Number of citations: 0
