The degree of frailty as a translational measure of health in aging (original) (raw)
Fontana, L., Kennedy, B. K., Longo, V. D., Seals, D. & Melov, S. Medical research: treat ageing. Nature511, 405–407 (2014). This influential commentary pithily summarized the geroscience agenda: "the problems of old age come as a package".
Epel, E. S. The geroscience agenda: toxic stress, hormetic stress and the rate of aging. Ageing Res. Rev.28, 101167 (2020). This paper calls to attention the role of hormetic stress in rates of aging. ArticleCAS Google Scholar
Davies, L. E. et al. Adverse outcomes of polypharmacy in older people: systematic review of reviews. J. Am. Med. Dir. Assoc.21, 181–187 (2020). ArticlePubMed Google Scholar
Eckart, A. et al. Validation of the hospital frailty risk score in a tertiary care hospital in Switzerland: results of a prospective, observational study. BMJ Open9, e026923 (2019). ArticlePubMedPubMed Central Google Scholar
Justice, J. N. et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine40, 554–563 (2019). This paper demonstrates that selectively ablating senescent cells with senolytic drugs can improve physical dysfunction in aging. ArticlePubMedPubMed Central Google Scholar
Hickson, L. J. et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine47, 446–456 (2019). ArticlePubMedPubMed Central Google Scholar
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell153, 1194–1217 (2013). This paper proposed that aging could be defined by characteristic features termed hallmarks. ArticlePubMedPubMed CentralCAS Google Scholar
Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell159, 709–713 (2014). This paper proposed that aging could be defined by characteristic features termed pillars. ArticlePubMedPubMed CentralCAS Google Scholar
Peters, R. et al. Common risk factors for major noncommunicable disease, a systematic overview of reviews and commentary: the implied potential for targeted risk reduction. Ther. Adv. Chronic Dis.10, 2040622319880392 (2019). ArticlePubMedPubMed Central Google Scholar
Abeliansky, A. L., Erel, D. & Strulik, H. Aging in the USA: similarities and disparities across time and space. Sci. Rep.10, 14309 (2020). This paper demonstrates the use of the frailty index as a biological foundation of health economic theory. ArticlePubMedPubMed CentralCAS Google Scholar
Hoogendijk, E. O. et al. Frailty: implications for clinical practice and public health. Lancet394, 1365–1375 (2019). ArticlePubMed Google Scholar
Rutenberg, A. D., Mitnitski, A. B., Farrell, S. G. & Rockwood, K. Unifying aging and frailty through complex dynamical networks. Exp. Gerontol.107, 126–129 (2018). ArticlePubMed Google Scholar
Arbeev, K. G. et al. Genetics of physiological dysregulation: findings from the long life family study using joint models. Aging12, 5920–5947 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Levine, M. E. Assessment of epigenetic clocks as biomarkers of aging in basic and population research. J. Gerontol. A Biol. Sci. Med. Sci.75, 463–465 (2020). ArticlePubMedPubMed Central Google Scholar
Li, X. et al. Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up. eLife9, e51507 (2020). This paper compared nine different measures of biological age, concluding that methylation age and frailty are complementary in predicting mortality.
Kameda, M., Mikawa, T., Yokode, M., Inagaki, N. & Kondoh, H. Senescence research from historical theory to future clinical application. Geriatr. Gerontol. Int.21, 125–130 (2021). ArticlePubMed Google Scholar
Rockwood, K. & Howlett, S. E. Age-related deficit accumulation and the diseases of ageing. Mech. Ageing Dev.180, 107–116 (2019). ArticlePubMed Google Scholar
Banga, S., Heinze-Milne, S. D. & Howlett, S. E. Rodent models of frailty and their application in preclinical research. Mech. Ageing Dev.179, 1–10 (2019). ArticlePubMed Google Scholar
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O. & Rockwood, K. Frailty in elderly people. Lancet381, 752–762 (2013). ArticlePubMed Google Scholar
Andrew, M. K. & Keefe, J. M. Social vulnerability from a social ecology perspective: a cohort study of older adults from the National Population Health Survey of Canada. BMC Geriatr.14, 90 (2014). ArticlePubMedPubMed Central Google Scholar
Gordon, E. H. & Hubbard, R. E. Differences in frailty in older men and women. Med. J. Aust.212, 183–188 (2020). ArticlePubMed Google Scholar
O’Caoimh, R. et al. Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies. Age Ageing50, 96–104 (2021). ArticlePubMed Google Scholar
Trendelenburg, A. U., Scheuren, A. C., Potter, P., Müller, R. & Bellantuono, I. Geroprotectors: a role in the treatment of frailty. Mech. Ageing Dev.180, 11–20 (2019). ArticlePubMedCAS Google Scholar
Negm, A. M. et al. Management of frailty: a systematic review and network meta-analysis of randomized controlled trials. J. Am. Med. Dir. Assoc.20, 1190–1198 (2019). ArticlePubMed Google Scholar
Adja, K. Y. C. et al. The importance of taking a patient-centered, community-based approach to preventing and managing frailty: a public health perspective. Front. Public Health8, 599170 (2020). ArticlePubMedPubMed Central Google Scholar
Navarrete-Villanueva, D. et al. Frailty and physical fitness in elderly people: a systematic review and meta-analysis. Sports Med.51, 143–160 (2021). ArticlePubMed Google Scholar
Rezaei-Shahsavarloo, Z., Atashzadeh-Shoorideh, F., Gobbens, R. J. J., Ebadi, A. & Harouni, G. G. The impact of interventions on management of frailty in hospitalized frail older adults: a systematic review and meta-analysis. BMC Geriatr.20, 526 (2020). ArticlePubMedPubMed Central Google Scholar
Konopka, A. R. et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell18, e12880 (2019). ArticlePubMedCAS Google Scholar
Feridooni, H. A. et al. The impact of age and frailty on ventricular structure and function in C57BL/6J mice. J. Physiol.595, 3721–3742 (2017). ArticlePubMedPubMed CentralCAS Google Scholar
Kane, A. E. et al. Age, sex and overall health, measured as frailty, modify myofilament proteins in hearts from naturally aging mice. Sci. Rep.10, 10052 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Vaupel, J. W., Manton, K. G. & Stallard, E. The impact of heterogeneity in individual frailty on the dynamics of mortality. Demography16, 439–454 (1979). This paper introduced the notion of variability in the rates of aging as defining frailty.
Hwang, S. W., Atia, M., Nisenbaum, R., Pare, D. E. & Joordens, S. Is looking older than one’s actual age a sign of poor health? J. Gen. Intern. Med.26, 136–141 (2011). ArticlePubMed Google Scholar
Fried, L. P. et al.; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci.56, M146–M156 (2001). This paper introduced the notion of the frailty syndrome as a phenotype.
Mitnitski, A. B., Mogilner, A. J. & Rockwood, K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal1, 323–336 (2001). This paper introduced the concept of frailty as a state defined by the accumulation of deficits. ArticlePubMedPubMed CentralCAS Google Scholar
Steverink, N., Slaets, J. P. J., Schuurmans, H. & Lis van, M. Measuring frailty. Development and testing of the Groningen Frailty Indicator (GFI). Gerontologist41, 236–237 (2001). Google Scholar
Dent, E., Kowal, P. & Hoogendijk, E. O. Frailty measurement in research and clinical practice: a review. Eur. J. Intern. Med.31, 3–10 (2016). ArticlePubMed Google Scholar
Gobbens, R. J., Boersma, P., Uchmanowicz, I. & Santiago, L. M. The Tilburg Frailty Indicator: new evidence for its validity. Clin. Interv. Aging15, 265–274 (2020). ArticlePubMedPubMed Central Google Scholar
Poh, A. W. Y. & Teo, S. P. Utility of frailty screening tools in older surgical patients. Ann. Geriatr. Med. Res.24, 75–82 (2020). ArticlePubMedPubMed Central Google Scholar
Searle, S. D., Mitnitski, A., Gahbauer, E. A., Gill, T. M. & Rockwood, K. A standard procedure for creating a frailty index. BMC Geriatr.8, 24 (2008). ArticlePubMedPubMed Central Google Scholar
Farrell, S. G., Mitnitski, A. B., Rockwood, K. & Rutenberg, A. D. Network model of human aging: frailty limits and information measures. Phys. Rev. E94, 052409 (2016). ArticlePubMed Google Scholar
Theou, O. et al. Modifications to the frailty phenotype criteria: systematic review of the current literature and investigation of 262 frailty phenotypes in the Survey of Health, Ageing and Retirement in Europe. Ageing Res. Rev.21, 78–94 (2015). ArticlePubMed Google Scholar
Morley, J. E., Malmstrom, T. K. & Miller, D. K. A simple frailty questionnaire (FRAIL) predicts outcomes in middle-aged African Americans. J. Nutr. Health Aging16, 601–608 (2012). ArticlePubMedPubMed CentralCAS Google Scholar
Panza, F. et al. Cognitive frailty: predementia syndrome and vascular risk factors. Neurobiol. Aging27, 933–940 (2006). ArticlePubMedCAS Google Scholar
Bunt, S., Steverink, N., Olthof, J., van der Schans, C. P. & Hobbelen, J. S. M. Social frailty in older adults: a scoping review. Eur. J. Ageing14, 323–334 (2017). ArticlePubMedPubMed CentralCAS Google Scholar
Howlett, S. E., Rockwood, M. R., Mitnitski, A. & Rockwood, K. Standard laboratory tests to identify older adults at increased risk of death. BMC Med.12, 171 (2014). This paper showed that the results of routine laboratory investigations can be combined to produce a frailty index with properties that suggest cellular and tissue deficits precede clinical features of frailty. ArticlePubMedPubMed Central Google Scholar
Johnson, R. L., McIsaac, D. I. & Mantilla, C. B. Preoperative frailty assessment: comment. Anesthesiology133, 468–470 (2020). ArticlePubMed Google Scholar
Kojima, G., Iliffe, S. & Walters, K. Frailty index as a predictor of mortality: a systematic review and meta-analysis. Age Ageing47, 193–200 (2018). ArticlePubMed Google Scholar
Kojima, G., Taniguchi, Y., Iliffe, S., Jivraj, S. & Walters, K. Transitions between frailty states among community-dwelling older people: a systematic review and meta-analysis. Ageing Res. Rev.50, 81–88 (2019). ArticlePubMed Google Scholar
Nguyen, Q. D. et al. Health heterogeneity in older adults: exploration in the Canadian Longitudinal Study on Aging. J. Am. Geriatr. Soc.69, 678–687 (2021). ArticlePubMed Google Scholar
Fan, J. et al. China Kadoorie Biobank Collaborative Group. Frailty index and all-cause and cause-specific mortality in Chinese adults: a prospective cohort study. Lancet Public Health5, e650–e660 (2020). ArticlePubMedPubMed Central Google Scholar
Kulminski, A. M. et al. Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study. J. Am. Geriatr. Soc.56, 898–903 (2008). ArticlePubMedPubMed Central Google Scholar
Ukraintseva, S., Yashin, A. I. & Arbeev, K. G. Resilience versus robustness in aging. J. Gerontol. A Biol. Sci. Med. Sci.71, 1533–1534 (2016). ArticlePubMedPubMed Central Google Scholar
Rolfson, D. B., Majumdar, S. R., Tsuyuki, R. T., Tahir, A. & Rockwood, K. Validity and reliability of the Edmonton Frail Scale. Age Ageing35, 526–529 (2006). ArticlePubMedPubMed Central Google Scholar
Parks, R. J. et al. A procedure for creating a frailty index based on deficit accumulation in aging mice. J. Gerontol. A Biol. Sci. Med. Sci.67, 217–227 (2012). This paper demonstrated that the concept of a frailty index could be applied to animal models. ArticlePubMed Google Scholar
Whitehead, J. C. et al. A clinical frailty index in aging mice: comparisons with frailty index data in humans. J. Gerontol. A Biol. Sci. Med. Sci.69, 621–632 (2014). ArticlePubMed Google Scholar
Liu, H., Graber, T. G., Ferguson-Stegall, L. & Thompson, L. V. Clinically relevant frailty index for mice. J. Gerontol. A Biol. Sci. Med. Sci.69, 1485–1491 (2014). ArticlePubMed Google Scholar
Hua, J. et al. Assessment of frailty in aged dogs. Am. J. Vet. Res.77, 1357–1365 (2016). ArticlePubMed Google Scholar
Yamada, Y. et al. Caloric restriction and healthy life span: frail phenotype of nonhuman primates in the Wisconsin national primate research center caloric restriction study. J. Gerontol. A Biol. Sci. Med. Sci.73, 273–278 (2018). ArticlePubMed Google Scholar
McNally, M. & Lahey, W. Frailty’s place in ethics and law: some thoughts on equality and autonomy and on limits and possibilities for aging citizens. Interdiscip. Top. Gerontol. Geriatr.41, 174–185 (2015). ArticlePubMed Google Scholar
Han, L., Clegg, A., Doran, T. & Fraser, L. The impact of frailty on health care resource use: a longitudinal analysis using the Clinical Practice Research Datalink in England. Age Ageing48, 665–671 (2019). This representative study suggests that per person cost to the health care system increases with the degree of frailty. ArticlePubMed Google Scholar
Granger, K., Ninan, S. & Stopford, E. The patient presenting with ‘acopia’. Acute Med.12, 173–177 (2013). ArticlePubMedCAS Google Scholar
Vermeiren, S. et al. Gerontopole Brussels Study group. Frailty and the prediction of negative health outcomes: a meta-analysis. J. Am. Med. Dir. Assoc.17, 1163.e1–1163.e17 (2016). Article Google Scholar
Shi, S. M., McCarthy, E. P., Mitchell, S. L. & Kim, D. H. Predicting mortality and adverse outcomes: comparing the frailty index to general prognostic indices. J. Gen. Intern. Med.35, 1516–1522 (2020). ArticlePubMedPubMed Central Google Scholar
Sillner, A. Y. et al. The association of a frailty index and incident delirium in older hospitalized patients: an observational cohort study. Clin. Interv. Aging15, 2053–2061 (2020). ArticlePubMedPubMed Central Google Scholar
Pérez-Zepeda, M. U., Carrillo-Vega, M. F., Theou, O., Jácome-Maldonado, L. D. & García-Peña, C. Hospital complications and frailty in Mexican older adults: an emergency care cohort analysis. Front. Med.7, 505 (2020). Article Google Scholar
Bowman, K. et al. Predicting incident delirium diagnoses using data from primary-care electronic health records. Age Ageing49, 374–381 (2020). ArticlePubMedPubMed Central Google Scholar
Hollinghurst, J. et al. External validation of the electronic Frailty Index using the population of Wales within the Secure Anonymised Information Linkage Databank. Age Ageing48, 922–926 (2019). ArticlePubMedPubMed Central Google Scholar
Kim, D. H. Measuring frailty in health care databases for clinical care and research. Ann. Geriatr. Med. Res.24, 62–74 (2020). ArticlePubMedPubMed Central Google Scholar
Simo, N. et al. Frailty index, hospital admission and number of days spent in hospital in nursing home residents: results from the INCUR study. J. Nutr. Health Aging25, 155–159 (2021). ArticlePubMedCAS Google Scholar
Know, C. S., Hasan, S. S., Thiruchelvam, K. & Aldeyab, M. Association of frailty and mortality in patients with COVID-19: a meta-analysis. Br. J. Anaesth.126, e108–e110 (2021). ArticleCAS Google Scholar
Pranata, R. et al. Clinical Frailty Scale and mortality in COVID-19: a systematic review and dose–response meta-analysis. Arch. Gerontol. Geriatr.93, 104324 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Hägg, S. et al. Age, frailty, and comorbidity as prognostic factors for short-term outcomes in patients with Coronavirus Disease 2019 in geriatric care. J. Am. Med. Dir. Assoc.21, 1555–1559 (2020). ArticlePubMedPubMed Central Google Scholar
Izurieta, H. S. et al. Natural history of COVID-19: risk factors for hospitalizations and deaths among >26 million US Medicare beneficiaries. J. Infect. Dis.223, 945–956 (2021). ArticlePubMedCAS Google Scholar
Cosco, T. D. et al. What is the relationship between validated frailty scores and mortality for adults with COVID-19 in acute hospital care? a systematic review. Age Ageing50, 608–616 (2021). ArticlePubMedPubMed Central Google Scholar
Petermann-Rocha, F. et al. Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank. BMC Med.18, 355 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Ma, Y. et al. The association between frailty and severe disease among COVID-19 patients aged over 60 years in China: a prospective cohort study. BMC Med.18, 274 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Vilches-Moraga, A. et al. COPE Study. Increased care at discharge from COVID-19: the association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study. BMC Med.18, 408 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Marengoni, A., Zucchelli, A., Grande, G., Fratiglioni, L. & Rizzuto, D. The impact of delirium on outcomes for older adults hospitalised with COVID-19. Age Ageing49, 923–926 (2020). ArticlePubMed Google Scholar
Kennedy, M. et al. Delirium in older patients with COVID-19 presenting to the emergency department. JAMA Netw. Open3, e2029540 (2020). ArticlePubMedPubMed Central Google Scholar
Persico, I. et al. Frailty and delirium in older adults: a systematic review and meta-analysis of the literature. J. Am. Geriatr. Soc.66, 2022–2030 (2018). ArticlePubMed Google Scholar
Aucoin, S. D. et al. Accuracy and feasibility of clinically applied frailty instruments before surgery: a systematic review and meta-analysis. Anesthesiology133, 78–95 (2020). ArticlePubMed Google Scholar
Geriatric Medicine Research Collaborative. Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: results of a prospective multi-centre study on World Delirium Awareness Day. BMC Med. 17, 229 (2019).
McElhaney, J. E. et al. The immune response to influenza in older humans: beyond immune senescence. Immun. Ageing17, 10 (2020). ArticlePubMedPubMed Central Google Scholar
Soiza, R. L., Scicluna, C. & Thomson, E. C. Efficacy and safety of COVID-19 vaccines in older people. Age Ageing50, 279–283 (2021). ArticlePubMed Google Scholar
Andrew, M. K. & McElhaney, J. E. Age and frailty in COVID-19 vaccine development. Lancet396, 1942–1944 (2021). ArticlePubMed Google Scholar
McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging and the Alzheimer’s Association Workgroup. Alzheimers Dement.7, 263–269 (2011). ArticlePubMedPubMed Central Google Scholar
Cummings, J. The National Institute on Aging-Alzheimer’s Association framework on Alzheimer’s disease: application to clinical trials. Alzheimers Dement.15, 172–178 (2019). ArticlePubMed Google Scholar
Nicoll, J. A. R. et al. Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer’s disease. Brain142, 2113–2126 (2019). ArticlePubMedPubMed Central Google Scholar
Holmes, C. et al. Long-term effects of Aβ42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet372, 216–223 (2008). ArticlePubMedCAS Google Scholar
Lim, A. et al. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J. Am. Geriatr. Soc.47, 564–569 (1999). ArticlePubMedCAS Google Scholar
Matthews, F. E. et al. Epidemiological pathology of dementia: attributable risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med.6, e1000180 (2009). ArticlePubMedPubMed Central Google Scholar
Brenowitz, W. D. et al. Alzheimer’s disease neuropathologic change, Lewy body disease and vascular brain injury in clinic- and community-based samples. Neurobiol. Aging53, 83–92 (2017). ArticlePubMedPubMed CentralCAS Google Scholar
Boyle, P. A. et al. Attributable risk of Alzheimer’s dementia attributed to age-related neuropathologies. Ann. Neurol.85, 114–124 (2019). ArticlePubMedCAS Google Scholar
Savva, G. M. et al. Age, neuropathology and dementia. N. Engl. J. Med.360, 2302–2309 (2009). ArticlePubMedCAS Google Scholar
Wallace, L. M. K. et al. Investigation of frailty as a moderator of the relationship between neuropathology and dementia in Alzheimer’s disease: a cross-sectional analysis of data from the Rush Memory and Aging Project. Lancet Neurol.18, 177–184 (2019). This paper demonstrates that frailty moderates the risk of Alzheimer neuropathology in relation to Alzheimer dementia in late life. ArticlePubMed Google Scholar
Mitnitski, A., Fallah, N., Rockwood, M. R. & Rockwood, K. Transitions in cognitive status in relation to frailty in older adults: a comparison of three frailty measures. J. Nutr. Health Aging15, 863–867 (2011). ArticlePubMedCAS Google Scholar
Song, X., Mitnitski, A. & Rockwood, K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurol77, 227–234 (2011). This paper introduced the notion of ‘traditional’ and ‘nontraditional’ risk factors for evaluating risk in relation to age-associated deficits. Article Google Scholar
Wallace, L. M. K. et al. Neuropathological burden and the degree of frailty in relation to global cognition and dementia. Neurology95, e3269–e3279 (2020). ArticlePubMedCASPubMed Central Google Scholar
Livingston, G. et al. Dementia prevention, intervention and care: 2020 report of the Lancet Commission. Lancet396, 413–446 (2020). ArticlePubMedPubMed Central Google Scholar
Wallace, L. M. et al. Accumulation of nontraditional risk factors for coronary heart disease is associated with incident coronary heart disease hospitalization and death. PLoS ONE9, e90475 (2014). ArticlePubMedPubMed CentralCAS Google Scholar
Dewan, P. et al. The prevalence and importance of frailty in heart failure with reduced ejection fraction—an analysis of PARADIGM-HF and ATMOSPHERE. Eur. J. Heart Fail.22, 2123–2133 (2020). ArticlePubMed Google Scholar
Farooqi, M. A. M., Gerstein, H., Yusuf, S. & Leong, D. P. Accumulation of deficits as a key risk factor for cardiovascular morbidity and mortality: a pooled analysis of 154,000 individuals. J. Am. Heart Assoc.9, e014686 (2020). This large-scale independent reanalysis of several clinical trials demonstrated the inseparability of deficit-driven, variable rates of aging from cardiovascular mortality. ArticlePubMedPubMed Central Google Scholar
Aguayo, G. A. et al. Comparative analysis of the association between 35 frailty scores and cardiovascular events, cancer and total mortality in an elderly general population in England: an observational study. PLoS Med.15, e1002543 (2018). ArticlePubMedPubMed Central Google Scholar
Wilkinson, C., Todd, O., Clegg, A., Gale, C. P. & Hall, M. Management of atrial fibrillation for older people with frailty: a systematic review and meta-analysis. Age Ageing48, 196–203 (2019). ArticlePubMed Google Scholar
Clegg, A. et al. Development and validation of an electronic frailty index using routine primary care electronic health record data. Age Ageing45, 353–360 (2016). This paper introduced an electronic frailty index collected from routine primary care practice visits, offering proof-of-concept of routine screening of the degree of frailty. ArticlePubMedPubMed Central Google Scholar
Wilkinson, C. et al. Atrial fibrillation and oral anticoagulation in older people with frailty: a nationwide primary care electronic health records cohort study. Age Ageing50, 772–779 (2021). ArticlePubMed Google Scholar
Wilkinson, C. et al. Clinical outcomes in patients with atrial fibrillation and frailty: insights from the ENGAGE AF-TIMI 48 trial. BMC Med.18, 401 (2020). ArticlePubMedPubMed Central Google Scholar
Warwick, J. et al. No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over. BMC Med.13, 78 (2015). ArticlePubMedPubMed Central Google Scholar
Pajewski, N. M. et al.; SPRINT Study Research Group. Characterizing frailty status in the systolic blood pressure intervention trial. J. Gerontol. A Biol. Sci. Med. Sci.71, 649–655 (2016).
Russo, G. et al. Impact of SPRINT results on hypertension guidelines: implications for ‘frail’ elderly patients. J. Hum. Hypertens.32, 633–638 (2018). ArticlePubMed Google Scholar
Benetos, A., Petrovic, M. & Strandberg, T. Hypertension management in older and frail older patients. Circ. Res.124, 1045–1060 (2019). ArticlePubMedCAS Google Scholar
Giffin, A., Madden, K. M. & Hogan, D. B. Blood pressure targets for older patients—do advanced age and frailty really not matter? Can. Geriatr. J.23, 205–209 (2020). ArticlePubMedPubMed Central Google Scholar
Bartosch, P., McGuigan, F. E. & Akesson, K. E. Progression of frailty and prevalence of osteoporosis in a community cohort of older women-a 10-year longitudinal study. Osteoporos. Int.29, 2191–2199 (2018). ArticlePubMedPubMed CentralCAS Google Scholar
Guaraldi, G. et al. A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. AIDS29, 1633–1641 (2015). ArticlePubMed Google Scholar
Legge, A. et al. Prediction of damage accrual in systemic lupus erythematosus using the systemic lupus international collaborating clinics frailty index. Arthritis Rheumatol.72, 658–666 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Herrera, A. P. et al. Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. Am. J. Public Health100, S105–S112 (2010). ArticlePubMedPubMed Central Google Scholar
Rich, M. W. et al.; American Heart Association Older Populations Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council; American College of Cardiology; and American Geriatrics Society. Knowledge gaps in cardiovascular care of the older adult population: a scientific statement from the American Heart Association, American College of Cardiology and American Geriatrics Society. J. Am. Coll. Cardiol.67, 2419–2440 (2016).
Walker, D. M. et al. Frailty and the management of patients with acute cardiovascular disease: a position paper from the Acute Cardiovascular Care Association. Eur. Heart J. Acute Cardiovasc. Care.7, 176–193 (2018). ArticlePubMedCAS Google Scholar
Hanlon, P. et al. Identifying frailty in trials: an analysis of individual participant data from trials of novel pharmacological interventions. BMC Med.18, 309 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Andrew, M. K., Mitnitski, A., Kirkland, S. A. & Rockwood, K. The impact of social vulnerability on the survival of the fittest older adults. Age Ageing41, 161–165 (2012). This paper proposes that the outcomes of the fittest people define the characteristics of a population or group, demonstrated here by the impact of social vulnerability on health and mortality.
Theou, O. et al. Exploring the relationship between national economic indicators and relative fitness and frailty in middle-aged and older Europeans. Age Ageing42, 614–619 (2013). ArticlePubMedPubMed Central Google Scholar
Shamliyan, T., Talley, K. M., Ramakrishnan, R. & Kane, R. L. Association of frailty with survival: a systematic literature review. Ageing Res. Rev.12, 719–736 (2013). ArticlePubMed Google Scholar
Ellis, H. L. et al. Complementing chronic frailty assessment at hospital admission with an electronic frailty index (FI-Laboratory) comprising routine blood test results. CMAJ192, E3–E8 (2020). ArticlePubMedPubMed Central Google Scholar
Abeliansky, A. L. & Strulik, H. Hungry children age faster. Econ. Hum. Biol.29, 211–220 (2018). ArticlePubMed Google Scholar
Marshall, A., Nazroo, J., Tampubolon, G. & Vanhoutte, B. Cohort differences in the levels and trajectories of frailty among older people in England. J. Epidemiol. Community Health69, 316–321 (2015). ArticlePubMed Google Scholar
Bäckman, K. et al. Changes in the lethality of frailty over 30 years: evidence from two cohorts of 70-year-olds in Gothenburg, Sweden. J. Gerontol. A Biol. Sci. Med. Sci.72, 945–950 (2017). PubMed Google Scholar
Mousa, A. et al. Is frailty a stable predictor of mortality across time? evidence from the cognitive function and ageing studies. Age Ageing47, 721–727 (2018). ArticlePubMedPubMed Central Google Scholar
Yu, R. et al. Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: an age–period–cohort analysis. Age Ageing47, 254–261 (2018). ArticlePubMed Google Scholar
Hoogendijk, E.O. et al. Trends in frailty and its association with mortality: results from the Longitudinal Aging Study Amsterdam, 1995–2016. Am. J. Epidemiol. https://doi.org/10.1093/aje/kwab018 (2021).
Haapanen, M. J. et al. Infant and childhood growth and frailty in old age: the Helsinki Birth Cohort Study. Aging Clin. Exp. Res.31, 717–721 (2019). ArticlePubMedCAS Google Scholar
Welstead, M. et al. Inflammation as a risk factor for the development of frailty in the Lothian Birth Cohort 1936. Exp. Gerontol.139, 111055 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Rockwood, K., Song, X. & Mitnitski, A. Changes in relative fitness and frailty across the adult life span: evidence from the Canadian National Population Health Survey. CMAJ183, E487–E494 (2011). ArticlePubMedPubMed Central Google Scholar
Blodgett, J. M., Rockwood, K. & Theou, O. Changes in the severity and lethality of age-related health deficit accumulation in the USA between 1999 and 2018: a population-based cohort study. Lancet Healthy Longev.2, E96–E104 (2021). Article Google Scholar
Brothers, T. D., Theou, O. & Rockwood, K. Frailty and migration in middle-aged and older Europeans. Arch. Gerontol. Geriatr.58, 63–68 (2014). ArticlePubMed Google Scholar
Franse, C. B. et al. Ethnic differences in frailty: a cross-sectional study of pooled data from community-dwelling older persons in the Netherlands. BMJ Open.8, e022241 (2018). ArticlePubMedPubMed Central Google Scholar
Pradhananga, S. et al. Ethnic differences in the prevalence of frailty in the United Kingdom assessed using the electronic Frailty Index. Aging Med.2, 168–173 (2019). Article Google Scholar
Herr, M., Robine, J. M., Aegerter, P., Arvieu, J. J. & Ankri, J. Contribution of socioeconomic position over life to frailty differences in old age: comparison of life-course models in a French sample of 2,350 old people. Ann. Epidemiol.25, 674–680 (2015). ArticlePubMed Google Scholar
Van der Linden, B. W. A. et al. Life-course socioeconomic conditions and frailty at older ages. J. Gerontol. B Psychol. Sci. Soc. Sci.75, 1348–1357 (2020). ArticlePubMed Google Scholar
Young, A. C., Glaser, K., Spector, T. D. & Steves, C. J. The identification of hereditary and environmental determinants of frailty in a cohort of UK twins. Twin Res. Hum. Genet.19, 600–609 (2016). This twin study suggests that about half of the interindividual variation in frailty is heritable. ArticlePubMed Google Scholar
Li, X. et al. The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards: a large cohort study. BMC Med.17, 94 (2019). ArticlePubMedPubMed Central Google Scholar
Raymond, E. et al. Drivers of frailty from adulthood into old age: results from a 27-year longitudinal population-based study in Sweden. J. Gerontol. A Biol. Sci. Med. Sci.75, 1943–1950 (2020). ArticlePubMedPubMed Central Google Scholar
Livshits, G. et al. Multi-omics analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways. Pain159, 2565–2572 (2018). ArticlePubMedPubMed CentralCAS Google Scholar
Taneja, S., Mitnitski, A. B., Rockwood, K. & Rutenberg, A. D. Dynamical network model for age-related health deficits and mortality. Phys. Rev. E93, 022309 (2016). The paper introduced a framework for modeling deficit accumulation and its relationship to mortality. ArticlePubMedCAS Google Scholar
Araújo Carvalho, A. C. et al. Telomere length and frailty in older adults—a systematic review and meta-analysis. Ageing Res. Rev.54, 100914 (2019). ArticlePubMedCAS Google Scholar
Hägg, S., Jylhävä, J., Wang, Y., Czene, K. & Grassmann, F. Deciphering the genetic and epidemiological landscape of mitochondrial DNA abundance. Hum. Genet.40, 849–861 (2021). This paper demonstrates that mitochondrial dysfunction is related to the degree of frailty in a sex-specific fashion. ArticleCAS Google Scholar
Hao, Q. et al. Prediction of mortality in Chinese very old people through the frailty index based on routine laboratory data. Sci. Rep.9, 221 (2019). ArticlePubMedPubMed CentralCAS Google Scholar
King, K. E., Fillenbaum, G. G. & Cohen, H. J. A cumulative deficit laboratory test-based frailty index: personal and neighborhood associations. J. Am. Geriatr. Soc.65, 1981–1987 (2017). ArticlePubMedPubMed Central Google Scholar
Mitnitski, A. & Rockwood, K. The rate of aging: the rate of deficit accumulation does not change over the adult life span. Biogerontology17, 199–204 (2016). ArticlePubMed Google Scholar
Hoogendijk, E. O. et al. Tracking changes in frailty throughout later life: results from a 17-year longitudinal study in the Netherlands. Age Ageing47, 727–733 (2018). ArticlePubMed Google Scholar
Stolz, E., Hoogendijk, E.O., Mayerl, H. & Freidl, W. Frailty changes predict mortality in four longitudinal studies of aging. J. Gerontol. A Biol. Sci. Med. Sci. https://doi.org/10.1093/gerona/glaa266 (2020).
Stolz, E. et al. Acceleration of health deficit accumulation in late life: evidence of terminal decline in frailty index three years before death in the US Health and Retirement Study. Ann. Epidemiol.58, 156–161 (2021). ArticlePubMed Google Scholar
Lu, W. et al. Relationship between employment histories and frailty trajectories in later life: evidence from the English Longitudinal Study of Ageing. J. Epidemiol. Community Health71, 439–445 (2017). ArticlePubMed Google Scholar
Noppert, G. A., Aiello, A. E., O’Rand, A. M. & Cohen, H. J. Race/ethnic and educational disparities in the association between pathogen burden and a laboratory-based cumulative deficits index. J. Racial Ethn. Health Disparities7, 99–108 (2020). ArticlePubMed Google Scholar
Miller, M. G., Thangthaeng, N. & Shukitt-Hale, B. A clinically relevant frailty index for aging rats. J. Gerontol. A Biol. Sci. Med. Sci.72, 892–896 (2017). ArticlePubMed Google Scholar
Rockwood, K. et al. A frailty index based on deficit accumulation quantifies mortality risk in humans and in mice. Sci. Rep.7, 43068 (2017). This paper demonstrates that deficits accumulate in similar patterns across the life course in humans and in mice. ArticlePubMedPubMed CentralCAS Google Scholar
Baumann, C. W., Kwak, D. & Thompson, L. V. Assessing onset, prevalence and survival in mice using a frailty phenotype. Aging10, 4042–4053 (2018). ArticlePubMedPubMed Central Google Scholar
Kwak, D., Baumann, C. W. & Thompson, L. V. Identifying characteristics of frailty in female mice using a phenotype assessment tool. J. Gerontol. A Biol. Sci. Med. Sci.75, 640–646 (2020). ArticlePubMedCAS Google Scholar
Yorke, A., Kane, A. E., Hancock Friesen, C. L., Howlett, S. E. & O’Blenes, S. Development of a rat clinical frailty index. J. Gerontol. A Biol. Sci. Med. Sci.72, 897–903 (2017). ArticlePubMedPubMed Central Google Scholar
Pandey, A., Kitzman, D. & Reeves, G. Frailty is intertwined with heart failure: mechanisms, prevalence, prognosis, assessment and management. JACC Heart Fail.7, 1001–1011 (2019). ArticlePubMedPubMed Central Google Scholar
Bibas, L. et al. Implications of frailty in elderly patients with electrophysiological conditions. JACC Clin. Electrophysiol.2, 288–294 (2016). ArticlePubMed Google Scholar
Yabuuchi, J. et al. Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease. Sci. Rep.10, 17647 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Antoch, M. P. et al. Physiological frailty index: quantitative in-life estimate of individual biological age in mice. Aging9, 615–626 (2017). ArticlePubMedPubMed CentralCAS Google Scholar
Keller, K., Kane, A. E., Heinze-Milne, S., Grandy, S. A. & Howlett, S. E. Chronic treatment with the ACE inhibitor enalapril attenuates the development of frailty and differentially modifies pro- and anti-inflammatory cytokines in aging male and female C57BL/6 mice. J. Gerontol. A Biol. Sci. Med. Sci.74, 1149–1157 (2019). This paper shows that long-term treatment of older mice with a drug that reduces inflammation improves health span. ArticlePubMedCAS Google Scholar
Kane, A. E., Keller, K. M., Heinze-Milne, S., Grandy, S. A. & Howlett, S. E. A murine frailty index based on clinical and laboratory measurements: links between frailty and pro-inflammatory cytokines differ in a sex-specific manner. J. Gerontol. A Biol. Sci. Med. Sci.74, 275–282 (2019). ArticlePubMedCAS Google Scholar
Wilson, D. et al. Frailty is associated with neutrophil dysfunction which is correctable with phosphoinositol-3-kinase inhibitors. J. Gerontol. A Biol. Sci. Med. Sci.75, 2320–2325 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Fulop, T. et al. Frailty, inflammation and immunosenescence. Interdiscip. Top. Gerontol. Geriatr.41, 26–40 (2015). ArticlePubMed Google Scholar
Graber, T. G., Ferguson-Stegall, L., Liu, H. & Thompson, L. V. Voluntary aerobic exercise reverses frailty in old mice. J. Gerontol. A Biol. Sci. Med. Sci.70, 1045–1058 (2015). ArticlePubMed Google Scholar
Gomez-Cabrera, M. C. et al. A new frailty score for experimental animals based on the clinical phenotype: inactivity as a model of frailty. J. Gerontol. A Biol. Sci. Med. Sci.72, 885–891 (2017). ArticlePubMed Google Scholar
Seldeen, K. L. et al. High-intensity interval training improves physical performance and frailty in aged mice. J. Gerontol. A Biol. Sci. Med. Sci.73, 429–437 (2018). ArticlePubMedCAS Google Scholar
Seldeen, K. L. et al. High-intensity interval training improves physical performance in aged female mice: a comparison of mouse frailty assessment tools. Mech. Ageing Dev.180, 49–62 (2019). ArticlePubMed Google Scholar
Kane, A. E. et al. Impact of longevity interventions on a validated mouse clinical frailty index. J. Gerontol. A Biol. Sci. Med. Sci.71, 333–339 (2016). ArticlePubMedCAS Google Scholar
Correia-Melo, C. et al. Rapamycin improves health span but not inflammaging in _Nfκb1_−/− mice. Aging Cell.18, e12882 (2019). ArticlePubMedCAS Google Scholar
Yu, D. et al. Calorie-restriction-induced insulin sensitivity is mediated by adipose mTORC2 and not required for life span extension. Cell Rep.29, 236–248 (2019). ArticlePubMed CentralCASPubMed Google Scholar
Richardson, N. E. et al. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice. Nat. Aging1, 73–86 (2021). ArticlePubMedPubMed Central Google Scholar
Henderson, Y.O. et al. Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner. Gerosciencehttps://doi.org/10.1007/s11357-021-00330-4 (2021).
Guderyon, M. J. et al. Mobilization-based transplantation of young-donor hematopoietic stem cells extends life span in mice. Aging Cell19, e13110 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Schultz, M. B. et al. Age and life expectancy clocks based on machine-learning analysis of mouse frailty. Nat. Commun.11, 4618 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Liu, Y. et al. Allicin reversed the process of frailty in aging male Fischer 344 rats with osteoporosis. J. Gerontol. A Biol. Sci. Med. Sci.75, 821–825 (2020). ArticlePubMedCAS Google Scholar
Asadi Shahmirzadi, A. et al. Alpha-ketoglutarate, an endogenous metabolite, extends life span and compresses morbidity in aging mice. Cell Metab.32, 447–456 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
Mach, J. et al. Chronic polypharmacy with increasing Drug Burden Index exacerbates frailty and impairs physical function, with effects attenuated by de-prescribing, in aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 76, 1010–1018 (2020).
Fielder, E. et al. Sublethal whole-body irradiation causes progressive premature frailty in mice. Mech. Ageing Dev.180, 63–69 (2019). ArticlePubMedPubMed Central Google Scholar
Darvall, J. N. et al. Frailty and outcomes from pneumonia in critical illness: a population-based cohort study. Br. J. Anaesth.125, 730–738 (2020). ArticlePubMedCAS Google Scholar
Pulok, M. H., Theou, O., van der Valk, A. M. & Rockwood, K. The role of illness acuity on the association between frailty and mortality in emergency department patients referred to internal medicine. Age Ageing49, 1071–1079 (2020). ArticlePubMedPubMed Central Google Scholar
Rockwood, K. & Mitnitski, A. Limits to deficit accumulation in elderly people. Mech. Ageing Dev.127, 494–496 (2006). ArticlePubMed Google Scholar
McIsaac, D. I., MacDonald, D. B. & Aucoin, S. D. Frailty for perioperative clinicians: a narrative review. Anesth. Analg.130, 1450–1460 (2020). ArticlePubMed Google Scholar
Carli, F., Bessissow, A., Awasthi, R. & Liberman, S. Prehabilitation: finally utilizing frailty screening data. Eur. J. Surg. Oncol.46, 321–325 (2020). ArticlePubMed Google Scholar
Coelho-Júnior, H. J. et al. Evidence-based recommendations for resistance and power training to prevent frailty in community-dwellers. Aging Clin. Exp. Res. 33, 2069–2086 (2021).
Guralnik, J. et al. Clinically meaningful change for physical performance: perspectives of the ICFSR Task Force. J. Frailty Aging9, 9–13 (2020). PubMedPubMed CentralCAS Google Scholar
Jang, I. Y. et al. Evaluation of clinically meaningful changes in measures of frailty. J. Gerontol. A Biol. Sci. Med. Sci.75, 1143–1147 (2020). ArticlePubMedPubMed Central Google Scholar
Theou, O. et al. Exploring clinically meaningful changes for the frailty index in a longitudinal cohort of hospitalized older patients. J. Gerontol. A Biol. Sci. Med. Sci.75, 1928–1934 (2020). ArticlePubMedPubMed Central Google Scholar
Hshieh, T. T., Yang, T., Gartaganis, S. L., Yue, J. & Inouye, S. K. Hospital elder life program: systematic review and meta-analysis of effectiveness. Am. J. Geriatr. Psychiatry26, 1015–1033 (2018). ArticlePubMedPubMed Central Google Scholar
Curtis, M. S., Forman, N. A., Donovan, A. L. & Whitlock, E. L. Postoperative delirium: why, what and how to confront it at your institution. Curr. Opin. Anaesthesiol.33, 668–673 (2020). ArticlePubMedPubMed Central Google Scholar
Khachaturian, A. S. et al. International drive to illuminate delirium: a developing public health blueprint for action. Alzheimers Dement.16, 711–725 (2020). ArticlePubMed Google Scholar
Rockwood, K. et al. CCCDTD5: reducing the risk of later-life dementia. Evidence informing the Fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD-5). Alzheimers Dement.6, e12083 (2020). Google Scholar
Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med.288, 518–536 (2020). ArticlePubMedCAS Google Scholar
Williams, D. M., Jylhävä, J., Pedersen, N. L., N.L. & Hägg, S. A frailty index for UK Biobank participants.J. Gerontol. A Biol. Sci. Med. Sci.74, 582–587 (2019). ArticlePubMed Google Scholar
Wang, Q. et al. Genetically predicted life-long lowering of low-density lipoprotein cholesterol is associated with decreased frailty: a Mendelian randomization study in UK biobank. EBioMedicine45, 487–494 (2019). ArticlePubMedPubMed Central Google Scholar
Mekli, K. Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom. PLoS ONE13, e0207824 (2018). ArticlePubMedPubMed CentralCAS Google Scholar
Espeland, M. A. et al.; Multimorbidity Clinical Trials Consortium. Clinical trials targeting aging and age-related multimorbidity.72, 355–361 (2017). J. Gerontol. A Biol. Sci. Med. Sci.72, 355–361 (2017).
Warner, H. R. et al. Program for testing biological interventions to promote healthy aging. Mech. Ageing Dev.115, 199–207 (2000). ArticlePubMedCAS Google Scholar
Farrell, S., Mitnitski, A., Rockwood, K. & Rutenberg, A. Generating synthetic aging trajectories with a weighted network model using cross-sectional data. Sci. Rep.10, 19833 (2020). ArticlePubMedPubMed CentralCAS Google Scholar
García-Peña, C. et al. Network analysis of frailty and aging: empirical data from the Mexican Health and Aging Study. Exp. Gerontol.128, 110747 (2019). ArticlePubMedPubMed Central Google Scholar
Stubbings, G., Farrell, S., Mitnitski, A., Rockwood, K. & Rutenberg, A. Informative frailty indices from binarized biomarkers. Biogerontology70, 1–11 (2020). Google Scholar
Farrell, S., Stubbings, G., Rockwood, K., Mitnitski, A. & Rutenberg, A. The potential for complex computational models of aging. Mech. Ageing Dev.193, 111403 (2021). ArticlePubMed Google Scholar