| Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. | |
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MedLine Citation:
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PMID: 19567825 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear. METHODS: Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures. RESULTS: Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems. CONCLUSIONS: Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty. |
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Authors:
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Linda P Fried; Qian-Li Xue; Anne R Cappola; Luigi Ferrucci; Paulo Chaves; Ravi Varadhan; Jack M Guralnik; Sean X Leng; Richard D Semba; Jeremy D Walston; Caroline S Blaum; Karen Bandeen-Roche |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-06-30 |
Journal Detail:
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Title: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 64 ISSN: 1758-535X ISO Abbreviation: J. Gerontol. A Biol. Sci. Med. Sci. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-04 Completed Date: 2009-09-29 Revised Date: 2010-10-04 |
Medline Journal Info:
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Nlm Unique ID: 9502837 Medline TA: J Gerontol A Biol Sci Med Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1049-57 Citation Subset: AIM; IM |
Affiliation:
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Columbia University, New York, NY 10032, USA. lpfried@columbia.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adiposity Aged Cohort Studies Dehydroepiandrosterone Sulfate / blood Female Frail Elderly Health Status* Hemoglobins / metabolism Homeostasis / physiology* Humans Insulin-Like Growth Factor I / metabolism Interleukin-6 / blood Micronutrients / blood Motor Skills / physiology Retrospective Studies Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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P30 AG021334/AG/NIA NIH HHS; R37 AG019905/AG/NIA NIH HHS; R37 AG019905-10/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hemoglobins; 0/Interleukin-6; 0/Micronutrients; 651-48-9/Dehydroepiandrosterone Sulfate; 67763-96-6/Insulin-Like Growth Factor I |
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