Frailty as a Clinically Relevant Measure of Human Aging

Article information

Ann Geriatr Med Res. 2021;25(3):139-140
Publication date (electronic) : 2021 September 27
doi : https://doi.org/10.4235/agmr.21.0106
Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Corresponding Author: Hee-Won Jung, MD, PhD Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Email dr.ecsta@gmail.com
Received 2021 September 13; Accepted 2021 September 25.

Frailty, commonly defined as a state of increased vulnerability to potential stressors with decreased physiological reserve owing to aging, has long been considered a geriatric syndrome.1-3) Research interest in frailty has increased following observations of vast inter-individual heterogeneities in accumulating deficits or functional impairments among functional or biological parameters with the progression of chronological aging.2) In the last three decades, researchers have attempted to capture frailty in various ways, from operational definitions to counting percentages of deficits arising owing to human aging.4-6) Although their methods of determining or quantifying frailty differ, studies have shown correlations between frailty spectrums defined by phenotype definition or deficit accumulation.7)

The clinical relevance of frailty as an aging phenotype has been validated with respect to multiple aspects. By incorporating age-related parameters that are also interconnected to form complex systems of human physiology,8) the burden of frailty in individuals reflects a systemic disturbance in response to various stressors.9) Population-based longitudinal studies have assessed the ability of the frailty index in predicting mortality, an unequivocal outcome indicator of human aging.10,11) Similarly, studies on patients with medical or surgical conditions have reported the superiority of the frailty spectrum in predicting adverse health outcomes compared with conventional measures.12-14) As a dynamic aging marker that responds to structured interventions, frailty is gradually becoming a cornerstone of geriatric medicine to deliver patient-centered management.15,16)

With recent advances in clinical and biological knowledge on frailty, the Annals of Geriatric Medicine and Research planned a special issue covering this geriatric syndrome from multifaceted aspects of biology, clinical medicine, and public health. In this issue, Ji et al.17) discussed frailty starting from molecular biology and demonstrated the validity of the frailty index as a measure of human aging compared to omics-based epigenetic clocks and biomarkers. Kwak18) discussed delirium, a geriatric giant and an important inpatient adverse outcome that occurs disproportionately in frail older people and can often be prevented by appropriate measures. Baek et al.19) reviewed the establishment and evolution of the Aging Study of Pyeongchang Rural Area (ASPRA), a cohort that was originally designed to determine the natural course of frailty in a Korean rural population and design effective interventional strategies that are feasible even in underserved regions in terms of healthcare resources.

The results of the studies support frailty as a clinically relevant measure of the human aging phenotype, with frailty a plastic and manageable geriatric syndrome. Unknowns still exist regarding the biology of frailty, which require further elucidation. While clinical interventions can improve frailty phenotypes and functional states, it remains unknown whether these improvements lead to the alleviation of the hallmarks of aging. Preclinical and early clinical studies have shown the potential to reverse or attenuate aging phenotypes with modalities related to energy metabolism or cellular senescence.20-22) These efforts have attracted research interest in rejuvenation and reverse-aging technologies. Moreover, the results of these studies revealed that some parameters of physical frailty improve with the underlying biological aging status.20) Geriatric interventions with proven clinical efficacies should be assessed with endpoints such as aging biomarkers to provide bi-directional evidence of the relationship between aging biology and frailty to eventually support the biological roles of geriatric interventions in the human aging spectrum.

Notes

CONFLICT OF INTEREST

Hee-Won Jung cofounded Dyphi Inc., a startup company on sensor technology.

FUNDING

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (No. 2021R1A2C300580111).

References

1. Mitnitski AB, Graham JE, Mogilner AJ, Rockwood K. Frailty, fitness and late-life mortality in relation to chronological and biological age. BMC Geriatr 2002;2:1.
2. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal 2001;1:323–36.
3. Jung HW. Visualizing domains of comprehensive geriatric assessments to grasp frailty spectrum in older adults with a radar chart. Ann Geriatr Med Res 2020;24:55–6.
4. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013;381:752–62.
5. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–56.
6. Howlett SE, Rutenberg AD, Rockwood K. The degree of frailty as a translational measure of health in aging. Nat Aging 2021;1:651–65.
7. Jung HW, Baek JY, Jang IY, Guralnik JM, Rockwood K, Lee E, et al. Short Physical Performance Battery as a crosswalk between frailty phenotype and deficit-accumulation frailty index. J Gerontol A Biol Sci Med Sci 2021;Mar. 29. [Epub]. https://doi.org/10.1093/gerona/glab087.
8. Farrell SG, Mitnitski AB, Rockwood K, Rutenberg AD. Network model of human aging: frailty limits and information measures. Phys Rev E 2016;94:052409.
9. Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173:489–95.
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. Lancet Public Health 2018;3:e323–e332.
11. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet 2019;394:1365–75.
12. Kastora S, Kounidas G, Perrott S, Carter B, Hewitt J, Myint PK. Clinical frailty scale as a point of care prognostic indicator of mortality in COVID-19: a systematic review and meta-analysis. EClinicalMedicine 2021;36:100896.
13. Kim SW, Han HS, Jung HW, Kim KI, Hwang DW, Kang SB, et al. Multidimensional frailty score for the prediction of postoperative mortality risk. JAMA Surg 2014;149:633–40.
14. Han SJ, Jung HW, Lee JH, Lim J, Moon SD, Yoon SW, et al. Clinical Frailty Scale, K-FRAIL questionnaire, and clinical outcomes in an acute hospitalist unit in Korea. Korean J Intern Med 2021;36:1233–41.
15. Jang IY, Jung HW, Lee HY, Park H, Lee E, Kim DH. Evaluation of clinically meaningful changes in measures of frailty. J Gerontol A Biol Sci Med Sci 2020;75:1143–7.
16. Park CM, Oh G, Lee H, Jung HW, Lee E, Jang IY, Kim DH. Multicomponent intervention and long-term disability in older adults: a nonrandomized prospective study. J Am Geriatr Soc 2021;69:669–77.
17. Ji L, Michal Jazwinski S, Kim S. Frailty and biological age. Ann Geriatr Med Res 2021;25:141–9.
18. Kwak MJ. Delirium in frail older adults. Ann Geriatr Med Res 2021;25:150–9.
19. Baek JY, Lee E, Oh G, Park YR, Lee H, Lim J, et al. The Aging Study of Pyeongchang Rural Area (ASPRA): findings and perspectives for human aging, frailty, and disability. Ann Geriatr Med Res 2021;25:160–9.
20. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011;479:232–6.
21. Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine 2019;40:554–63.
22. Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013;4:2192.

Article information Continued