A Comparative Review of Frailty Models and a description of the European-wide FRAILOMIC Initiative: designed to promote Healthy Aging

Background Frailty in aging populations is associated with increasing evidence of ill health, functional loss, increasing dependency and premature death. The FRAILOMIC Initiative was designed to define, predict and prevent frailty by means of identifying omic markers associated with the diagnosis, risk, and prognosis of frailty. The project hopes to build the foundations for a consensus towards a single operative, clinical definition of frailty to guide the development of ready-to-use kits measuring biomarkers to facilitate frailty risk prediction and improve diagnostic accuracy of frailty in clinical practice. Aims We review current models of frailty, describe the design of the FRAILOMIC study, and discuss the advent of the concept of intrinsic capacity as influencing the science of frailty and how this can be clinically interpreted. Methods Two main frailty models (Fried Phenotype model; Cumulative Deficit Model) are described and evaluated by detailed literature review. A description of the exploratory phase of the FRAILOMIC initiative is given which resulted in the identification of 13 omic markers related to frailty: these are currently being validated in a validation phase. We then discuss how combining the characteristics of frailty with omic-based biomarkers will enable the development of predictive, diagnostic and prognostic models. Conclusions Relating biomarkers associated with frailty to a continuous measure of intrinsic capacity will help in identifying and monitoring at-risk populations. The FRAILOMIC Initiative will provide key insights into the prevention, early detection, and treatment of frailty to reduce the impact of disability in our aging populations.

[1]  L. Rodríguez-Mañas,et al.  Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. , 2016, Molecular aspects of medicine.

[2]  L. Fried,et al.  Frailty in older adults: evidence for a phenotype. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  G. Hankey,et al.  Associations of insulin‐like growth factor‐I and its binding proteins and testosterone with frailty in older men , 2013, Clinical endocrinology.

[4]  G. Wang,et al.  Immunologic Changes in Frail Older Adults , 2014, Translational medicine @ UniSa.

[5]  J. Spagnoli,et al.  Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries , 2013, BMC Geriatrics.

[6]  Ritu Sadana,et al.  The World report on ageing and health: a policy framework for healthy ageing , 2016, The Lancet.

[7]  J. Dartigues,et al.  Dietary Patterns and 12-Year Risk of Frailty: Results From the Three-City Bordeaux Study. , 2017, Journal of the American Medical Directors Association.

[8]  A. Sinclair,et al.  The Third Transition: The Clinical Evolution Oriented to the Contemporary Older Patient. , 2017, Journal of the American Medical Directors Association.

[9]  T. Strandberg,et al.  Frailty in elderly people , 2007, The Lancet.

[10]  J. Dartigues,et al.  Higher Protein but Not Energy Intake Is Associated With a Lower Prevalence of Frailty Among Community-Dwelling Older Adults in the French Three-City Cohort. , 2016, Journal of the American Medical Directors Association.

[11]  Linda P Fried,et al.  Frailty in the clinical scenario , 2015, The Lancet.

[12]  A. Mitnitski,et al.  Frailty in relation to the accumulation of deficits. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[13]  Jesper Tegnér,et al.  Detecting multivariate differentially expressed genes , 2007, BMC Bioinformatics.

[14]  Aaron Aragaki,et al.  Frailty: Emergence and Consequences in Women Aged 65 and Older in the Women's Health Initiative Observational Study , 2005, Journal of the American Geriatrics Society.

[15]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[16]  L. Rodríguez-Mañas,et al.  The Standardization of Frailty Phenotype Criteria Improves Its Predictive Ability: The Toledo Study for Healthy Aging. , 2017, Journal of the American Medical Directors Association.

[17]  Ronei Silveira Pinto,et al.  Strength and endurance training prescription in healthy and frail elderly. , 2014, Aging and disease.

[18]  M. Cesari,et al.  Components of the Frailty Phenotype in Relation to the Frailty Index: Results From the Toulouse Frailty Platform. , 2015, Journal of the American Medical Directors Association.

[19]  K. Walters,et al.  Prevalence of frailty in Japan: A systematic review and meta-analysis , 2016, Journal of epidemiology.

[20]  A. Scuteri,et al.  Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss. , 2013, International journal of cardiology.

[21]  Kenneth Rockwood,et al.  What would make a definition of frailty successful? , 2005, Age and ageing.

[22]  M.W.G. Nijhuis-van der Sanden,et al.  Outcome instruments to measure frailty: A systematic review , 2011, Ageing Research Reviews.

[23]  A. B. Mitnitski,et al.  Aging, frailty and complex networks , 2017, Biogerontology.

[24]  M. Fisher,et al.  Sarcopenia in aging humans: the impact of menopause and disease. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[25]  Kenneth Rockwood,et al.  Prevalence and 10‐Year Outcomes of Frailty in Older Adults in Relation to Deficit Accumulation , 2010, Journal of the American Geriatrics Society.

[26]  Y. Wu,et al.  Effect of exercise on physical function, daily living activities, and quality of life in the frail older adults: a meta-analysis. , 2012, Archives of physical medicine and rehabilitation.

[27]  B. Graubard,et al.  Prevention and Epidemiology , 2022 .

[28]  J. Michel,et al.  Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[29]  Sara Espinoza,et al.  Frailty in older adults: insights and interventions. , 2005, Cleveland Clinic journal of medicine.

[30]  D. Schlessinger,et al.  Associations of large artery structure and function with adiposity: effects of age, gender, and hypertension. The SardiNIA Study. , 2012, Atherosclerosis.

[31]  L. Rodríguez-Mañas,et al.  Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease. , 2016, Journal of the American Medical Directors Association.

[32]  J. Egido,et al.  Proteomic strategies in the search of new biomarkers in atherothrombosis. , 2010, Journal of the American College of Cardiology.

[33]  L. Rodríguez-Mañas,et al.  Pharmaceutical interventions for frailty and sarcopenia. , 2014, Current pharmaceutical design.

[34]  Anthony A. Vandervoort,et al.  The Effectiveness of Exercise Interventions for the Management of Frailty: A Systematic Review , 2011, Journal of aging research.

[35]  J. Egido,et al.  Atorvastatin modifies the protein profile of circulating human monocytes after an acute coronary syndrome , 2009, Proteomics.

[36]  Kenneth Rockwood,et al.  Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. , 2013, The journals of gerontology. Series A, Biological sciences and medical sciences.

[37]  M. Serrano Senescence helps regeneration. , 2014, Developmental cell.

[38]  Jesper Tegnér,et al.  On reliable discovery of molecular signatures , 2009, BMC Bioinformatics.

[39]  Matteo Cesari,et al.  The frailty phenotype and the frailty index: different instruments for different purposes. , 2014, Age and ageing.

[40]  Jesper Tegnér,et al.  Laboratory biomarkers and frailty: presentation of the FRAILOMIC initiative , 2015, Clinical chemistry and laboratory medicine.

[41]  L. Rodríguez-Mañas,et al.  The frailty syndrome in the public health agenda , 2014, Journal of Epidemiology & Community Health.

[42]  L. Ferrucci,et al.  The central arterial burden of the metabolic syndrome is similar in men and women: the SardiNIA Study. , 2010, European heart journal.

[43]  L. Ferrucci,et al.  Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. , 2003, The Journal of clinical endocrinology and metabolism.

[44]  H. Amièva,et al.  Frailty among community-dwelling elderly people in France: the three-city study. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[45]  K. Rockwood,et al.  Frailty in NHANES: Comparing the frailty index and phenotype. , 2015, Archives of gerontology and geriatrics.

[46]  I. Lang,et al.  Frailty, body mass index, and abdominal obesity in older people. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[47]  M. Cesari,et al.  Frailty and Multimorbidity: Different Ways of Thinking About Geriatrics. , 2017, Journal of the American Medical Directors Association.

[48]  J. Egido,et al.  Improving metabolite knowledge in stable atherosclerosis patients by association and correlation of GC-MS and 1H NMR fingerprints. , 2009, Journal of proteome research.

[49]  Jesper Tegnér,et al.  Reading Dependencies from the Minimal Undirected Independence Map of a Graphoid that Satisfies Weak Transitivity , 2009, Probabilistic Graphical Models.

[50]  Kathleen Koenig,et al.  Serum Interleukin‐6 and Hemoglobin as Physiological Correlates in the Geriatric Syndrome of Frailty: A Pilot Study , 2002, Journal of the American Geriatrics Society.

[51]  L. Rodríguez-Mañas,et al.  A new operational definition of frailty: the Frailty Trait Scale. , 2014, Journal of the American Medical Directors Association.

[52]  Brent C Taylor,et al.  Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. , 2008, Archives of internal medicine.